diff --git a/lib/galaxy/datatypes/dataproviders/hierarchy.py b/lib/galaxy/datatypes/dataproviders/hierarchy.py
index e0773975548f..6ee9d5b992c4 100644
--- a/lib/galaxy/datatypes/dataproviders/hierarchy.py
+++ b/lib/galaxy/datatypes/dataproviders/hierarchy.py
@@ -3,7 +3,10 @@
 """
 import logging
 
-from galaxy.util import etree
+from galaxy.util import (
+    Element,
+    etree,
+)
 from . import line
 
 _TODO = """
@@ -65,7 +68,6 @@ def matches_selector(self, element, selector=None):
         # TODO: add more flexibility here w/o re-implementing xpath
         # TODO: fails with '#' - browser thinks it's an anchor - use urlencode
         # TODO: need removal/replacement of etree namespacing here - then move to string match
-        Element = getattr(etree, "_Element", etree.Element)
         return bool((selector is None) or (isinstance(element, Element) and selector in element.tag))
 
     def element_as_dict(self, element):
diff --git a/lib/galaxy/dependencies/__init__.py b/lib/galaxy/dependencies/__init__.py
index 0cfa3f7148ea..17aa22c8d60d 100644
--- a/lib/galaxy/dependencies/__init__.py
+++ b/lib/galaxy/dependencies/__init__.py
@@ -67,18 +67,15 @@ def load_job_config_dict(job_conf_dict):
                 job_conf_path = join(dirname(self.config_file), job_conf_path)
             if ".xml" in job_conf_path:
                 try:
-                    try:
-                        for plugin in parse_xml(job_conf_path).find("plugins").findall("plugin"):
+                    job_conf_tree = parse_xml(job_conf_path)
+                    plugins_elem = job_conf_tree.find("plugins")
+                    if plugins_elem:
+                        for plugin in plugins_elem.findall("plugin"):
                             if "load" in plugin.attrib:
                                 self.job_runners.append(plugin.attrib["load"])
-                    except OSError:
-                        pass
-                    try:
-                        for plugin in parse_xml(job_conf_path).findall('.//destination/param[@id="rules_module"]'):
-                            self.job_rule_modules.append(plugin.text)
-                    except OSError:
-                        pass
-                except etree.ParseError:
+                    for plugin in job_conf_tree.findall('.//destination/param[@id="rules_module"]'):
+                        self.job_rule_modules.append(plugin.text)
+                except (OSError, etree.ParseError):
                     pass
             else:
                 try:
diff --git a/lib/galaxy/dependencies/pinned-typecheck-requirements.txt b/lib/galaxy/dependencies/pinned-typecheck-requirements.txt
index 77f07fd86ab1..2bd9345bf304 100644
--- a/lib/galaxy/dependencies/pinned-typecheck-requirements.txt
+++ b/lib/galaxy/dependencies/pinned-typecheck-requirements.txt
@@ -1,6 +1,7 @@
 annotated-types==0.6.0 ; python_version >= "3.8" and python_version < "3.13"
 cffi==1.16.0 ; python_version >= "3.8" and python_version < "3.13"
 cryptography==41.0.7 ; python_version >= "3.8" and python_version < "3.13"
+lxml-stubs==0.5.1 ; python_version >= "3.8" and python_version < "3.13"
 mypy-extensions==1.0.0 ; python_version >= "3.8" and python_version < "3.13"
 mypy==1.8.0 ; python_version >= "3.8" and python_version < "3.13"
 pycparser==2.21 ; python_version >= "3.8" and python_version < "3.13"
diff --git a/lib/galaxy/jobs/__init__.py b/lib/galaxy/jobs/__init__.py
index 48a22bae5d10..6ae85cb7e34f 100644
--- a/lib/galaxy/jobs/__init__.py
+++ b/lib/galaxy/jobs/__init__.py
@@ -79,7 +79,6 @@
     ToolEvaluator,
 )
 from galaxy.util import (
-    etree,
     parse_xml_string,
     RWXRWXRWX,
     safe_makedirs,
@@ -643,7 +642,7 @@ def get_tool_resource_xml(self, tool_id, tool_type):
                             field_name, self.resource_parameters
                         )
                         raise KeyError(message)
-                    fields.append(etree.fromstring(self.resource_parameters[field_name]))
+                    fields.append(parse_xml_string(self.resource_parameters[field_name]))
 
                 if fields:
                     conditional_element = parse_xml_string(self.JOB_RESOURCE_CONDITIONAL_XML)
diff --git a/lib/galaxy/jobs/dynamic_tool_destination.py b/lib/galaxy/jobs/dynamic_tool_destination.py
index 53664b33ece5..9e61e9adb88f 100755
--- a/lib/galaxy/jobs/dynamic_tool_destination.py
+++ b/lib/galaxy/jobs/dynamic_tool_destination.py
@@ -1647,14 +1647,14 @@ def get_destination_list_from_job_config(job_config_location) -> set:
 
         # Add all destination IDs from the job configuration xml file
         for destination in job_conf.getroot().iter("destination"):
-            if isinstance(destination.get("id"), str):
-                destination_list.add(destination.get("id"))
-
+            destination_id = destination.get("id")
+            if destination_id:
+                destination_list.add(destination_id)
             else:
                 error = f"Destination ID '{str(destination)}"
                 error += "' in job configuration file cannot be"
                 error += " parsed. Things may not work as expected!"
-                log.debug(error)
+                log.warning(error)
 
     return destination_list
 
diff --git a/lib/galaxy/jobs/runners/util/cli/job/torque.py b/lib/galaxy/jobs/runners/util/cli/job/torque.py
index 56754b142b58..84273f2fce1d 100644
--- a/lib/galaxy/jobs/runners/util/cli/job/torque.py
+++ b/lib/galaxy/jobs/runners/util/cli/job/torque.py
@@ -1,4 +1,8 @@
 from logging import getLogger
+from typing import (
+    Dict,
+    Union,
+)
 
 from galaxy.util import parse_xml_string
 from . import (
@@ -64,7 +68,7 @@ def get_status(self, job_ids=None):
     def get_single_status(self, job_id):
         return f"qstat -f {job_id}"
 
-    def parse_status(self, status, job_ids):
+    def parse_status(self, status: str, job_ids) -> Union[Dict, None]:
         # in case there's noise in the output, find the big blob 'o xml
         tree = None
         rval = {}
@@ -80,11 +84,15 @@ def parse_status(self, status, job_ids):
             return None
         else:
             for job in tree.findall("Job"):
-                id = job.find("Job_Id").text
-                if id in job_ids:
-                    state = job.find("job_state").text
+                job_id_elem = job.find("Job_Id")
+                assert job_id_elem
+                id_ = job_id_elem.text
+                if id_ in job_ids:
+                    job_state_elem = job.find("job_state")
+                    assert job_state_elem
+                    state = job_state_elem.text
                     # map PBS job states to Galaxy job states.
-                    rval[id] = self._get_job_state(state)
+                    rval[id_] = self._get_job_state(state)
         return rval
 
     def parse_single_status(self, status, job_id):
diff --git a/lib/galaxy/tool_shed/galaxy_install/tools/data_manager.py b/lib/galaxy/tool_shed/galaxy_install/tools/data_manager.py
index f2cbcdc072af..95af11b21f53 100644
--- a/lib/galaxy/tool_shed/galaxy_install/tools/data_manager.py
+++ b/lib/galaxy/tool_shed/galaxy_install/tools/data_manager.py
@@ -111,8 +111,8 @@ def install_data_managers(
                     data_manager_id = elem.get("id", None)
                     if data_manager_id is None:
                         log.error(
-                            "A data manager was defined that does not have an id and will not be installed:\n%s"
-                            % xml_to_string(elem)
+                            "A data manager was defined that does not have an id and will not be installed:\n%s",
+                            xml_to_string(elem),
                         )
                         continue
                     data_manager_dict = (
@@ -170,7 +170,7 @@ def install_data_managers(
                     )
                     if data_manager:
                         rval.append(data_manager)
-                elif elem.tag is etree.Comment:
+                elif elem.tag is etree.Comment:  # type: ignore[comparison-overlap]
                     pass
                 else:
                     log.warning(f"Encountered unexpected element '{elem.tag}':\n{xml_to_string(elem)}")
diff --git a/lib/galaxy/tool_shed/galaxy_install/tools/tool_panel_manager.py b/lib/galaxy/tool_shed/galaxy_install/tools/tool_panel_manager.py
index e4d1dc3c19bd..0db2a88562ea 100644
--- a/lib/galaxy/tool_shed/galaxy_install/tools/tool_panel_manager.py
+++ b/lib/galaxy/tool_shed/galaxy_install/tools/tool_panel_manager.py
@@ -13,8 +13,9 @@
 from galaxy.tool_shed.util.repository_util import get_repository_owner
 from galaxy.tool_shed.util.shed_util_common import get_tool_panel_config_tool_path_install_dir
 from galaxy.util import (
-    etree,
+    Element,
     parse_xml_string,
+    SubElement,
     xml_to_string,
 )
 from galaxy.util.renamed_temporary_file import RenamedTemporaryFile
@@ -154,27 +155,27 @@ def config_elems_to_xml_file(self, config_elems, config_filename, tool_path, too
 
     def generate_tool_elem(
         self, tool_shed, repository_name, changeset_revision, owner, tool_file_path, tool, tool_section
-    ):
+    ) -> Element:
         """Create and return an ElementTree tool Element."""
         if tool_section is not None:
-            tool_elem = etree.SubElement(tool_section, "tool")
+            tool_elem = SubElement(tool_section, "tool")
         else:
-            tool_elem = etree.Element("tool")
+            tool_elem = Element("tool")
         tool_elem.attrib["file"] = tool_file_path
         if not tool.guid:
             raise ValueError("tool has no guid")
         tool_elem.attrib["guid"] = tool.guid
-        tool_shed_elem = etree.SubElement(tool_elem, "tool_shed")
+        tool_shed_elem = SubElement(tool_elem, "tool_shed")
         tool_shed_elem.text = tool_shed
-        repository_name_elem = etree.SubElement(tool_elem, "repository_name")
+        repository_name_elem = SubElement(tool_elem, "repository_name")
         repository_name_elem.text = repository_name
-        repository_owner_elem = etree.SubElement(tool_elem, "repository_owner")
+        repository_owner_elem = SubElement(tool_elem, "repository_owner")
         repository_owner_elem.text = owner
-        changeset_revision_elem = etree.SubElement(tool_elem, "installed_changeset_revision")
+        changeset_revision_elem = SubElement(tool_elem, "installed_changeset_revision")
         changeset_revision_elem.text = changeset_revision
-        id_elem = etree.SubElement(tool_elem, "id")
+        id_elem = SubElement(tool_elem, "id")
         id_elem.text = tool.id
-        version_elem = etree.SubElement(tool_elem, "version")
+        version_elem = SubElement(tool_elem, "version")
         version_elem.text = tool.version
         return tool_elem
 
@@ -297,7 +298,7 @@ def generate_tool_panel_elem_list(
         owner="",
     ):
         """Generate a list of ElementTree Element objects for each section or tool."""
-        elem_list: List[etree.Element] = []
+        elem_list: List[Element] = []
         tool_elem = None
         cleaned_repository_clone_url = remove_protocol_and_user_from_clone_url(repository_clone_url)
         if not owner:
@@ -335,6 +336,7 @@ def generate_tool_panel_elem_list(
                     tool_section if inside_section else None,
                 )
                 if inside_section:
+                    assert tool_section
                     if section_in_elem_list is not None:
                         elem_list[section_in_elem_list] = tool_section
                     else:
@@ -366,17 +368,13 @@ def generate_tool_section_dicts(self, tool_config=None, tool_sections=None) -> L
             tool_section_dicts.append(dict(tool_config=tool_config, id="", version="", name=""))
         return tool_section_dicts
 
-    def generate_tool_section_element_from_dict(self, tool_section_dict):
+    def generate_tool_section_element_from_dict(self, tool_section_dict: Dict[str, str]) -> Element:
         # The value of tool_section_dict looks like the following.
         # { id: <ToolSection id>, version : <ToolSection version>, name : <TooSection name>}
-        if tool_section_dict["id"]:
-            # Create a new tool section.
-            tool_section = etree.Element("section")
-            tool_section.attrib["id"] = tool_section_dict["id"]
-            tool_section.attrib["name"] = tool_section_dict["name"]
-            tool_section.attrib["version"] = tool_section_dict["version"]
-        else:
-            tool_section = None
+        tool_section = Element("section")
+        tool_section.attrib["id"] = tool_section_dict["id"]
+        tool_section.attrib["name"] = tool_section_dict["name"]
+        tool_section.attrib["version"] = tool_section_dict["version"]
         return tool_section
 
     def get_or_create_tool_section(self, toolbox, tool_panel_section_id, new_tool_panel_section_label=None):
diff --git a/lib/galaxy/tool_shed/metadata/metadata_generator.py b/lib/galaxy/tool_shed/metadata/metadata_generator.py
index 71d3f666f7ad..a93139c17afd 100644
--- a/lib/galaxy/tool_shed/metadata/metadata_generator.py
+++ b/lib/galaxy/tool_shed/metadata/metadata_generator.py
@@ -492,9 +492,9 @@ def generate_repository_dependency_metadata(self, repository_dependencies_config
             root = tree.getroot()
             xml_is_valid = root.tag == "repositories"
         if xml_is_valid:
-            invalid_repository_dependencies_dict = dict(description=root.get("description"))
+            invalid_repository_dependencies_dict: Dict[str, Any] = dict(description=root.get("description"))
             invalid_repository_dependency_tups = []
-            valid_repository_dependencies_dict = dict(description=root.get("description"))
+            valid_repository_dependencies_dict: Dict[str, Any] = dict(description=root.get("description"))
             valid_repository_dependency_tups = []
             for repository_elem in root.findall("repository"):
                 repository_dependency_tup, repository_dependency_is_valid, err_msg = self.handle_repository_elem(
diff --git a/lib/galaxy/tool_shed/tools/data_table_manager.py b/lib/galaxy/tool_shed/tools/data_table_manager.py
index 4ca5dcfdc5d1..f5d0a5669a7d 100644
--- a/lib/galaxy/tool_shed/tools/data_table_manager.py
+++ b/lib/galaxy/tool_shed/tools/data_table_manager.py
@@ -9,7 +9,10 @@
 
 from galaxy.tool_shed.galaxy_install.client import InstallationTarget
 from galaxy.tool_shed.util import hg_util
-from galaxy.util import etree
+from galaxy.util import (
+    Element,
+    SubElement,
+)
 from galaxy.util.tool_shed import xml_util
 
 if TYPE_CHECKING:
@@ -29,24 +32,24 @@ def __init__(self, app: RequiredAppT):
 
     def generate_repository_info_elem(
         self, tool_shed: str, repository_name: str, changeset_revision: str, owner: str, parent_elem=None, **kwd
-    ) -> etree.Element:
+    ) -> Element:
         """Create and return an ElementTree repository info Element."""
         if parent_elem is None:
-            elem = etree.Element("tool_shed_repository")
+            elem = Element("tool_shed_repository")
         else:
-            elem = etree.SubElement(parent_elem, "tool_shed_repository")
-        tool_shed_elem = etree.SubElement(elem, "tool_shed")
+            elem = SubElement(parent_elem, "tool_shed_repository")
+        tool_shed_elem = SubElement(elem, "tool_shed")
         tool_shed_elem.text = tool_shed
-        repository_name_elem = etree.SubElement(elem, "repository_name")
+        repository_name_elem = SubElement(elem, "repository_name")
         repository_name_elem.text = repository_name
-        repository_owner_elem = etree.SubElement(elem, "repository_owner")
+        repository_owner_elem = SubElement(elem, "repository_owner")
         repository_owner_elem.text = owner
-        changeset_revision_elem = etree.SubElement(elem, "installed_changeset_revision")
+        changeset_revision_elem = SubElement(elem, "installed_changeset_revision")
         changeset_revision_elem.text = changeset_revision
         # add additional values
         # TODO: enhance additional values to allow e.g. use of dict values that will recurse
         for key, value in kwd.items():
-            new_elem = etree.SubElement(elem, key)
+            new_elem = SubElement(elem, key)
             new_elem.text = value
         return elem
 
diff --git a/lib/galaxy/tool_util/data/__init__.py b/lib/galaxy/tool_util/data/__init__.py
index 77f03cf9c7e0..06e0aafe033e 100644
--- a/lib/galaxy/tool_util/data/__init__.py
+++ b/lib/galaxy/tool_util/data/__init__.py
@@ -169,8 +169,9 @@ def __init__(
         filename: Optional[StrPath] = None,
         other_config_dict: Optional[StoresConfigFilePaths] = None,
     ) -> None:
-        self.name = config_element.get("name")
-        self.comment_char = config_element.get("comment_char")
+        name = config_element.get("name")
+        assert name
+        self.name = name
         self.empty_field_value = config_element.get("empty_field_value", "")
         self.empty_field_values: Dict[str, str] = {}
         self.allow_duplicate_entries = util.asbool(config_element.get("allow_duplicate_entries", True))
@@ -179,7 +180,7 @@ def __init__(
         self.tool_data_path = tool_data_path
         self.tool_data_path_files = tool_data_path_files
         self.other_config_dict = other_config_dict or {}
-        self.missing_index_file = None
+        self.missing_index_file: Optional[str] = None
         # increment this variable any time a new entry is added, or when the table is totally reloaded
         # This value has no external meaning, and does not represent an abstract version of the underlying data
         self._loaded_content_version = 1
@@ -348,11 +349,19 @@ def configure_and_load(
         # store repo info if available:
         repo_elem = config_element.find("tool_shed_repository")
         if repo_elem is not None:
+            tool_shed_elem = repo_elem.find("tool_shed")
+            assert tool_shed_elem
+            repository_name_elem = repo_elem.find("repository_name")
+            assert repository_name_elem
+            repository_owner_elem = repo_elem.find("repository_owner")
+            assert repository_owner_elem
+            installed_changeset_revision_elem = repo_elem.find("installed_changeset_revision")
+            assert installed_changeset_revision_elem
             repo_info = dict(
-                tool_shed=repo_elem.find("tool_shed").text,
-                name=repo_elem.find("repository_name").text,
-                owner=repo_elem.find("repository_owner").text,
-                installed_changeset_revision=repo_elem.find("installed_changeset_revision").text,
+                tool_shed=tool_shed_elem.text,
+                name=repository_name_elem.text,
+                owner=repository_owner_elem.text,
+                installed_changeset_revision=installed_changeset_revision_elem.text,
             )
         else:
             repo_info = None
@@ -375,12 +384,13 @@ def configure_and_load(
                     tmp_file.flush()
                 else:
                     # Pull the filename from a global config
-                    filename = file_element.get("from_config", None) or None
+                    filename = file_element.get("from_config")
                     if filename:
                         filename = self.other_config_dict.get(filename, None)
-            filename = file_path = _expand_here_template(filename, here=self.here)
+            if filename:
+                filename = _expand_here_template(filename, here=self.here)
             found = False
-            if file_path is None:
+            if filename is None:
                 log.debug(
                     "Encountered a file element (%s) that does not contain a path value when loading tool data table '%s'.",
                     util.xml_to_string(file_element),
@@ -399,7 +409,7 @@ def configure_and_load(
                 # regular galaxy app has and uses tool_data_path.
                 # We're loading a tool in the tool shed, so we cannot use the Galaxy tool-data
                 # directory which is hard-coded into the tool_data_table_conf.xml entries.
-                filename = os.path.split(file_path)[1]
+                filename = os.path.split(filename)[1]
                 filename = os.path.join(tool_data_path, filename)
             if self.tool_data_path_files.exists(filename):
                 found = True
@@ -526,11 +536,11 @@ def parse_column_spec(self, config_element: Element) -> None:
         else:
             self.largest_index = 0
             for column_elem in config_element.findall("column"):
-                name = column_elem.get("name", None)
+                name = column_elem.get("name")
                 assert name is not None, "Required 'name' attribute missing from column def"
-                index = column_elem.get("index", None)
-                assert index is not None, "Required 'index' attribute missing from column def"
-                index = int(index)
+                index_attr = column_elem.get("index")
+                assert index_attr is not None, "Required 'index' attribute missing from column def"
+                index = int(index_attr)
                 self.columns[name] = index
                 if index > self.largest_index:
                     self.largest_index = index
diff --git a/lib/galaxy/tool_util/data/bundles/models.py b/lib/galaxy/tool_util/data/bundles/models.py
index d37bd6d86c24..730c51c216f3 100644
--- a/lib/galaxy/tool_util/data/bundles/models.py
+++ b/lib/galaxy/tool_util/data/bundles/models.py
@@ -167,11 +167,11 @@ def _xml_to_data_table_output_column_move(move_elem: Element) -> DataTableBundle
         source_value = ""
     else:
         source_base = source_elem.get("base", None)
-        source_value = source_elem.text
+        source_value = source_elem.text or ""
     target_elem = move_elem.find("target")
     if target_elem is None:
         target_base = None
-        target_value = ""
+        target_value: Optional[str] = ""
     else:
         target_base = target_elem.get("base", None)
         target_value = target_elem.text
diff --git a/lib/galaxy/tool_util/lint.py b/lib/galaxy/tool_util/lint.py
index 44ab28b9790e..54390031a232 100644
--- a/lib/galaxy/tool_util/lint.py
+++ b/lib/galaxy/tool_util/lint.py
@@ -57,7 +57,7 @@
 
 from galaxy.tool_util.parser import get_tool_source
 from galaxy.util import (
-    etree,
+    Element,
     submodules,
 )
 
@@ -102,7 +102,7 @@ def __repr__(self) -> str:
 
 
 class XMLLintMessageLine(LintMessage):
-    def __init__(self, level: str, message: str, node: Optional[etree.Element] = None):
+    def __init__(self, level: str, message: str, node: Optional[Element] = None):
         super().__init__(level, message)
         self.line = None
         if node is not None:
@@ -118,7 +118,7 @@ def __str__(self) -> str:
 
 
 class XMLLintMessageXPath(LintMessage):
-    def __init__(self, level: str, message: str, node: Optional[etree.Element] = None):
+    def __init__(self, level: str, message: str, node: Optional[Element] = None):
         super().__init__(level, message)
         self.xpath = None
         if node is not None:
diff --git a/lib/galaxy/tool_util/parser/xml.py b/lib/galaxy/tool_util/parser/xml.py
index 96b3634c333b..5c723c3a851f 100644
--- a/lib/galaxy/tool_util/parser/xml.py
+++ b/lib/galaxy/tool_util/parser/xml.py
@@ -93,7 +93,6 @@ def destroy_tree(tree):
 def parse_change_format(change_format: Iterable[Element]) -> List[ChangeFormatModel]:
     change_models: List[ChangeFormatModel] = []
     for change_elem in change_format:
-        change_elem = cast(Element, change_elem)
         for when_elem in change_elem.findall("when"):
             when_elem = cast(Element, when_elem)
             value: Optional[str] = when_elem.get("value", None)
@@ -123,7 +122,6 @@ class XmlToolSource(ToolSource):
     """Responsible for parsing a tool from classic Galaxy representation."""
 
     language = "xml"
-    root: Element
 
     def __init__(self, xml_tree: ElementTree, source_path=None, macro_paths=None):
         self.xml_tree = xml_tree
diff --git a/lib/galaxy/tool_util/toolbox/base.py b/lib/galaxy/tool_util/toolbox/base.py
index a146c93cde26..006fa8302a23 100644
--- a/lib/galaxy/tool_util/toolbox/base.py
+++ b/lib/galaxy/tool_util/toolbox/base.py
@@ -661,6 +661,7 @@ def _load_integrated_tool_panel_keys(self):
                 section = ToolSection(elem)
                 for section_elem in elem:
                     section_id = section_elem.get("id")
+                    assert section_id
                     if section_elem.tag == "tool":
                         section.elems.stub_tool(section_id)
                     elif section_elem.tag == "workflow":
diff --git a/lib/galaxy/tool_util/verify/__init__.py b/lib/galaxy/tool_util/verify/__init__.py
index 364aa46489b4..83e6a2c3fd23 100644
--- a/lib/galaxy/tool_util/verify/__init__.py
+++ b/lib/galaxy/tool_util/verify/__init__.py
@@ -69,7 +69,7 @@ def get_filename(filename: str) -> str:
     assertions = attributes.get("assert_list", None)
     if attributes is not None and assertions is not None:
         try:
-            verify_assertions(output_content, attributes["assert_list"], attributes.get("decompress"))
+            verify_assertions(output_content, attributes["assert_list"], attributes.get("decompress", False))
         except AssertionError as err:
             errmsg = f"{item_label} different than expected\n"
             errmsg += unicodify(err)
diff --git a/lib/galaxy/tool_util/verify/asserts/__init__.py b/lib/galaxy/tool_util/verify/asserts/__init__.py
index 1589b4b0c18d..3d34e5bdb18d 100644
--- a/lib/galaxy/tool_util/verify/asserts/__init__.py
+++ b/lib/galaxy/tool_util/verify/asserts/__init__.py
@@ -32,7 +32,7 @@
             assertion_functions[member] = value
 
 
-def verify_assertions(data: bytes, assertion_description_list, decompress=None):
+def verify_assertions(data: bytes, assertion_description_list, decompress: bool = False):
     """This function takes a list of assertions and a string to check
     these assertions against."""
     if decompress:
diff --git a/lib/galaxy/tool_util/verify/asserts/xml.py b/lib/galaxy/tool_util/verify/asserts/xml.py
index bdb53e3913e8..b80798436e2e 100644
--- a/lib/galaxy/tool_util/verify/asserts/xml.py
+++ b/lib/galaxy/tool_util/verify/asserts/xml.py
@@ -129,7 +129,7 @@ def assert_xml_element(
         if attribute is None or attribute == "":
             content = occ.text
         else:
-            content = occ.attrib[attribute]
+            content = occ.attrib[attribute]  # type: ignore[assignment] # https://github.com/lxml/lxml-stubs/pull/99
         try:
             verify_assertions_function(content, children)
         except AssertionError as e:
diff --git a/lib/galaxy/tools/__init__.py b/lib/galaxy/tools/__init__.py
index 5831359a8411..a3b894d1e9b8 100644
--- a/lib/galaxy/tools/__init__.py
+++ b/lib/galaxy/tools/__init__.py
@@ -26,7 +26,6 @@
 from urllib.parse import unquote_plus
 
 import webob.exc
-from lxml import etree
 from mako.template import Template
 from packaging.version import Version
 from sqlalchemy import (
@@ -150,6 +149,7 @@
     listify,
     Params,
     parse_xml_string,
+    parse_xml_string_to_etree,
     rst_to_html,
     string_as_bool,
     unicodify,
@@ -535,7 +535,7 @@ def create_tool(self, config_file, tool_cache_data_dir=None, **kwds):
             if tool_document:
                 tool_source = self.get_expanded_tool_source(
                     config_file=config_file,
-                    xml_tree=etree.ElementTree(etree.fromstring(tool_document["document"].encode("utf-8"))),
+                    xml_tree=parse_xml_string_to_etree(tool_document["document"]),
                     macro_paths=tool_document["macro_paths"],
                 )
             else:
diff --git a/lib/galaxy/tools/data_manager/manager.py b/lib/galaxy/tools/data_manager/manager.py
index 1c8d6c7b92b6..8da9f8e97f9e 100644
--- a/lib/galaxy/tools/data_manager/manager.py
+++ b/lib/galaxy/tools/data_manager/manager.py
@@ -35,7 +35,7 @@ def __init__(self, app: StructuredApp, xml_filename=None, reload_count: Optional
         self.app = app
         self.data_managers = {}
         self.managed_data_tables = {}
-        self.tool_path = None
+        self.tool_path: Optional[str] = None
         self.__reload_count = reload_count or 0
         self.filename = xml_filename or self.app.config.data_manager_config_file
         for filename in util.listify(self.filename):
@@ -143,13 +143,13 @@ class DataManager:
 
     tool: Optional[Tool]
 
-    def __init__(self, data_managers: DataManagers, elem: Element = None, tool_path: Optional[str] = None):
+    def __init__(self, data_managers: DataManagers, elem: Optional[Element] = None, tool_path: Optional[str] = None):
         self.data_managers = data_managers
-        self.declared_id = None
-        self.name = None
-        self.description = None
+        self.declared_id: Optional[str] = None
+        self.name: Optional[str] = None
+        self.description: Optional[str] = None
         self.version = self.DEFAULT_VERSION
-        self.guid = None
+        self.guid: Optional[str] = None
         self.tool = None
         self.tool_shed_repository_info: Optional[RepoInfo] = None
         self.undeclared_tables = False
diff --git a/lib/galaxy/util/__init__.py b/lib/galaxy/util/__init__.py
index 2f19adcf8cd5..8d8b51f445c3 100644
--- a/lib/galaxy/util/__init__.py
+++ b/lib/galaxy/util/__init__.py
@@ -35,9 +35,12 @@
 from os.path import relpath
 from typing import (
     Any,
+    cast,
+    Dict,
     Iterable,
     Iterator,
     List,
+    Mapping,
     Optional,
     overload,
     Tuple,
@@ -58,7 +61,10 @@
 )
 from requests.adapters import HTTPAdapter
 from requests.packages.urllib3.util.retry import Retry  # type: ignore[import-untyped]
-from typing_extensions import Literal
+from typing_extensions import (
+    Literal,
+    Self,
+)
 
 try:
     import grp
@@ -68,22 +74,52 @@
 LXML_AVAILABLE = True
 try:
     from lxml import etree
-    from lxml.etree import _Element as Element
+
+    # lxml.etree.Element is a function that returns a new instance of the
+    # lxml.etree._Element class. This class doesn't have a proper __init__()
+    # method, so we can add a __new__() constructor that mimicks the
+    # xml.etree.ElementTree.Element initialization.
+    class Element(etree._Element):
+        def __new__(cls, tag, attrib={}, **extra) -> Self:  # noqa: B006
+            return cast(Self, etree.Element(tag, attrib, **extra))
+
+        def __iter__(self) -> Iterator[Self]:  # type: ignore[override]
+            return cast(Iterator[Self], super().__iter__())
+
+        def find(self, path: str, namespaces: Optional[Mapping[str, str]] = None) -> Union[Self, None]:
+            ret = super().find(path, namespaces)
+            if ret is not None:
+                return cast(Self, ret)
+            else:
+                return None
+
+        def findall(self, path: str, namespaces: Optional[Mapping[str, str]] = None) -> List[Self]:  # type: ignore[override]
+            return cast(List[Self], super().findall(path, namespaces))
+
+    def SubElement(parent: Element, tag: str, attrib: Optional[Dict[str, str]] = None, **extra) -> Element:
+        return cast(Element, etree.SubElement(parent, tag, attrib, **extra))
 
     # lxml.etree.ElementTree is a function that returns a new instance of the
-    # lxml.etree._ElementTree class. This class doesn't have a proper
-    # __init__() method, so we can add a __new__() constructor that mimicks
+    # lxml.etree._ElementTree class. This class doesn't have a proper __init__()
+    # method, so we can add a __new__() constructor that mimicks the
     # xml.etree.ElementTree.ElementTree initialization.
     class ElementTree(etree._ElementTree):
-        def __new__(cls, element=None, file=None) -> etree.ElementTree:
-            return etree.ElementTree(element, file=file)
+        def __new__(cls, element=None, file=None) -> Self:
+            return cast(Self, etree.ElementTree(element, file=file))
+
+        def getroot(self) -> Element:
+            return cast(Element, super().getroot())
+
+    def XML(text: Union[str, bytes]) -> Element:
+        return cast(Element, etree.XML(text))
 
 except ImportError:
     LXML_AVAILABLE = False
     import xml.etree.ElementTree as etree  # type: ignore[assignment,no-redef]
-    from xml.etree.ElementTree import (  # type: ignore[assignment]
+    from xml.etree.ElementTree import (  # type: ignore[assignment]  # noqa: F401
         Element,
         ElementTree,
+        XML,
     )
 
 from .custom_logging import get_logger
@@ -129,8 +165,6 @@ def shlex_join(split_command):
 RWXR_XR_X = stat.S_IRWXU | stat.S_IRGRP | stat.S_IXGRP | stat.S_IROTH | stat.S_IXOTH
 RWXRWXRWX = stat.S_IRWXU | stat.S_IRWXG | stat.S_IRWXO
 
-XML = etree.XML
-
 defaultdict = collections.defaultdict
 
 UNKNOWN = "unknown"
@@ -311,7 +345,7 @@ def parse_xml(
             schema = etree.XMLSchema(schema_root)
 
     try:
-        tree = etree.parse(str(fname), parser=parser)
+        tree = cast(ElementTree, etree.parse(str(fname), parser=parser))
         root = tree.getroot()
         if strip_whitespace:
             for elem in root.iter("*"):
@@ -337,10 +371,11 @@ def parse_xml(
 
 def parse_xml_string(xml_string: str, strip_whitespace: bool = True) -> Element:
     try:
-        elem = etree.fromstring(xml_string)
+        elem = XML(xml_string)
     except ValueError as e:
         if "strings with encoding declaration are not supported" in unicodify(e):
-            elem = etree.fromstring(xml_string.encode("utf-8"))
+            # This happens with lxml for a string that starts with e.g. `<?xml version="1.0" encoding="UTF-8"?>`
+            elem = XML(xml_string.encode("utf-8"))
         else:
             raise e
     if strip_whitespace:
diff --git a/lib/galaxy/util/tool_shed/xml_util.py b/lib/galaxy/util/tool_shed/xml_util.py
index b7bc8fba1ac3..0aee018cd5e4 100644
--- a/lib/galaxy/util/tool_shed/xml_util.py
+++ b/lib/galaxy/util/tool_shed/xml_util.py
@@ -7,9 +7,9 @@
 )
 
 from galaxy.util import (
-    etree,
+    Element,
+    ElementTree,
     parse_xml as galaxy_parse_xml,
-    unicodify,
     xml_to_string,
 )
 from galaxy.util.path import StrPath
@@ -17,7 +17,7 @@
 log = logging.getLogger(__name__)
 
 
-def create_and_write_tmp_file(elem: etree.Element) -> str:
+def create_and_write_tmp_file(elem: Element) -> str:
     tmp_str = xml_to_string(elem, pretty=True)
     with tempfile.NamedTemporaryFile(prefix="tmp-toolshed-cawrf", delete=False) as fh:
         tmp_filename = fh.name
@@ -26,7 +26,7 @@ def create_and_write_tmp_file(elem: etree.Element) -> str:
     return tmp_filename
 
 
-def parse_xml(file_name: StrPath, check_exists=True) -> Tuple[Optional[etree.ElementTree], str]:
+def parse_xml(file_name: StrPath, check_exists=True) -> Tuple[Optional[ElementTree], str]:
     """Returns a parsed xml tree with comments intact."""
     error_message = ""
     if check_exists and not os.path.exists(file_name):
@@ -36,7 +36,7 @@ def parse_xml(file_name: StrPath, check_exists=True) -> Tuple[Optional[etree.Ele
     except OSError:
         raise
     except Exception as e:
-        error_message = f"Exception attempting to parse {str(file_name)}: {unicodify(e)}"
+        error_message = f"Exception attempting to parse {file_name}: {e}"
         log.exception(error_message)
         return None, error_message
     return tree, error_message
diff --git a/lib/galaxy_test/selenium/test_workflow_editor.py b/lib/galaxy_test/selenium/test_workflow_editor.py
index caa5de321d0c..d8bdd2c34018 100644
--- a/lib/galaxy_test/selenium/test_workflow_editor.py
+++ b/lib/galaxy_test/selenium/test_workflow_editor.py
@@ -1110,8 +1110,10 @@ def test_editor_place_comments(self):
         # check if all options were applied
         comment_content: WebElement = editor.comment.text_inner.wait_for_visible()
         assert comment_content.text == "Hello World"
-        assert "bold" in comment_content.get_attribute("class")
-        assert "italic" in comment_content.get_attribute("class")
+        comment_content_class = comment_content.get_attribute("class")
+        assert comment_content_class
+        assert "bold" in comment_content_class
+        assert "italic" in comment_content_class
 
         # check for correct size
         width, height = self.get_element_size(editor.comment._.wait_for_visible())
diff --git a/lib/tool_shed/dependencies/attribute_handlers.py b/lib/tool_shed/dependencies/attribute_handlers.py
index ea611b132ab8..e581137bdb4f 100644
--- a/lib/tool_shed/dependencies/attribute_handlers.py
+++ b/lib/tool_shed/dependencies/attribute_handlers.py
@@ -10,7 +10,8 @@
 
 from galaxy.util import (
     asbool,
-    etree,
+    Element,
+    SubElement,
 )
 from tool_shed.dependencies.tool import tag_attribute_handler
 from tool_shed.repository_types.util import (
@@ -228,13 +229,13 @@ def _create_element(
     tag: str,
     attributes: Optional[Dict[str, str]] = None,
     sub_elements: Optional[Dict[str, List[Tuple[str, str]]]] = None,
-) -> Optional[etree.Element]:
+) -> Optional[Element]:
     """
     Create a new element whose tag is the value of the received tag, and whose attributes are all
     key / value pairs in the received attributes and sub_elements.
     """
     if tag:
-        elem = etree.Element(tag)
+        elem = Element(tag)
         if attributes:
             # The received attributes is an odict to preserve ordering.
             for k, attribute_value in attributes.items():
@@ -247,14 +248,14 @@ def _create_element(
                 if v:
                     if k == "packages":
                         # The received sub_elements is an odict whose key is 'packages' and whose
-                        # value is a list of ( name, version ) tuples.
+                        # value is a list of (name, version) tuples.
                         for v_tuple in v:
-                            sub_elem = etree.SubElement(elem, "package")
+                            sub_elem = SubElement(elem, "package")
                             sub_elem_name, sub_elem_version = v_tuple
                             sub_elem.set("name", sub_elem_name)
                             sub_elem.set("version", sub_elem_version)
                     elif isinstance(v, list):
-                        sub_elem = etree.SubElement(elem, k)
+                        sub_elem = SubElement(elem, k)
                         # If v is a list, then it must be a list of tuples where the first
                         # item is the tag and the second item is the text value.
                         for v_tuple in v:
@@ -263,10 +264,10 @@ def _create_element(
                                 v_text = v_tuple[1]
                                 # Don't include fields that are blank.
                                 if v_text:
-                                    v_elem = etree.SubElement(sub_elem, v_tag)
+                                    v_elem = SubElement(sub_elem, v_tag)
                                     v_elem.text = v_text
                     else:
-                        sub_elem = etree.SubElement(elem, k)
+                        sub_elem = SubElement(elem, k)
                         sub_elem.text = v
         return elem
     return None
diff --git a/pyproject.toml b/pyproject.toml
index f72a74981b4e..6ce683587e31 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -166,6 +166,7 @@ watchdog = "*"
 
 [tool.poetry.group.typecheck.dependencies]
 mypy = "*"
+lxml-stubs = "*"
 pydantic = ">=2"  # for pydantic.mypy plugin
 types-bleach = "*"
 types-boto = "*"
diff --git a/test/unit/app/queue_worker/conftest.py b/test/unit/app/queue_worker/conftest.py
index 3849e7b86904..af918f0b44ab 100644
--- a/test/unit/app/queue_worker/conftest.py
+++ b/test/unit/app/queue_worker/conftest.py
@@ -7,7 +7,7 @@
 try:
     import psycopg
 except ImportError:
-    psycopg = None
+    psycopg = None  # type: ignore[assignment]
 
 try:
     import psycopg2
diff --git a/test/unit/tool_util/data/test_tool_data_bundles.py b/test/unit/tool_util/data/test_tool_data_bundles.py
index 9c6afddc5735..c607876de30c 100644
--- a/test/unit/tool_util/data/test_tool_data_bundles.py
+++ b/test/unit/tool_util/data/test_tool_data_bundles.py
@@ -28,6 +28,7 @@ def test_xml_parsing() -> None:
     tree = parse_xml(path)
     data_managers_el = tree.getroot()
     data_manager_el = data_managers_el.find("data_manager")
+    assert data_manager_el
     description = convert_data_tables_xml(data_manager_el)
     assert not description.undeclared_tables
     assert len(description.data_tables) == 1
@@ -58,6 +59,7 @@ def test_parsing_manual() -> None:
         tree = parse_xml(path)
     data_managers_el = tree.getroot()
     data_manager_el = data_managers_el.find("data_manager")
+    assert data_manager_el
     description = convert_data_tables_xml(data_manager_el)
     assert description.undeclared_tables
     assert len(description.data_tables) == 0
@@ -68,6 +70,7 @@ def test_parsing_mothur() -> None:
         tree = parse_xml(path)
     data_managers_el = tree.getroot()
     data_manager_el = data_managers_el.find("data_manager")
+    assert data_manager_el
     description = convert_data_tables_xml(data_manager_el)
     assert not description.undeclared_tables
     assert len(description.data_tables) == 4
diff --git a/test/unit/tool_util/verify/test_asserts.py b/test/unit/tool_util/verify/test_asserts.py
index cb415507c530..22d5b67b23f7 100644
--- a/test/unit/tool_util/verify/test_asserts.py
+++ b/test/unit/tool_util/verify/test_asserts.py
@@ -2,6 +2,7 @@
 import os
 import shutil
 import tempfile
+from typing import Tuple
 
 try:
     import h5py
@@ -10,7 +11,7 @@
 
 from galaxy.tool_util.parser.xml import __parse_assert_list_from_elem
 from galaxy.tool_util.verify import asserts
-from galaxy.util import etree
+from galaxy.util import parse_xml_string
 
 TABULAR_ASSERTION = """
     <assert_contents>
@@ -1314,8 +1315,8 @@ def test_has_h5_attribute_failure():
         assert len(a) == 1
 
 
-def run_assertions(assertion_xml, data, decompress=None):
-    assertion = etree.fromstring(assertion_xml)
+def run_assertions(assertion_xml: str, data, decompress=False) -> Tuple:
+    assertion = parse_xml_string(assertion_xml)
     assertion_description = __parse_assert_list_from_elem(assertion)
     try:
         asserts.verify_assertions(data, assertion_description, decompress=decompress)