diff --git a/changelog/736.feature.rst b/changelog/736.feature.rst
new file mode 100644
index 00000000..e6ce4e10
--- /dev/null
+++ b/changelog/736.feature.rst
@@ -0,0 +1 @@
+Eliminated dependency on Setuptools/pkg_resources and replaced with packaging and importlib_metadata.
diff --git a/mypy.ini b/mypy.ini
index 504e01fe..81394f10 100644
--- a/mypy.ini
+++ b/mypy.ini
@@ -22,6 +22,9 @@ strict_equality = True
 ; https://github.com/tartley/colorama/issues/206
 ignore_missing_imports = True
 
+[mypy-packaging]
+ignore_missing_imports = True
+
 [mypy-pkginfo]
 ; https://bugs.launchpad.net/pkginfo/+bug/1876591
 ignore_missing_imports = True
@@ -37,10 +40,6 @@ ignore_missing_imports = True
 [mypy-rfc3986]
 ignore_missing_imports = True
 
-[mypy-setuptools]
-; https://github.com/python/typeshed/issues/2171
-ignore_missing_imports = True
-
 [mypy-tqdm]
 ; https://github.com/tqdm/tqdm/issues/260
 ignore_missing_imports = True
diff --git a/setup.cfg b/setup.cfg
index f47de473..46f8fe2b 100644
--- a/setup.cfg
+++ b/setup.cfg
@@ -38,7 +38,7 @@ install_requires=
     readme_renderer >= 21.0
     requests >= 2.20
     requests-toolbelt >= 0.8.0, != 0.9.0
-    setuptools >= 0.7.0
+    packaging >= 16.2
     tqdm >= 4.14
     importlib_metadata >= 3.6
     keyring >= 15.1
diff --git a/tests/fixtures/twine-3.3.0-py3.9.egg b/tests/fixtures/twine-3.3.0-py3.9.egg
new file mode 100644
index 00000000..d0088a5e
Binary files /dev/null and b/tests/fixtures/twine-3.3.0-py3.9.egg differ
diff --git a/tests/test_package.py b/tests/test_package.py
index b9ea4335..c6de1976 100644
--- a/tests/test_package.py
+++ b/tests/test_package.py
@@ -264,3 +264,8 @@ def test_malformed_from_file(monkeypatch):
         package_file.PackageFile.from_filename(filename, comment=None)
 
     assert "Invalid distribution file" in err.value.args[0]
+
+
+def test_package_from_egg():
+    filename = "tests/fixtures/twine-3.3.0-py3.9.egg"
+    package_file.PackageFile.from_filename(filename, comment=None)
diff --git a/tests/test_repository.py b/tests/test_repository.py
index 97639835..91c0d19a 100644
--- a/tests/test_repository.py
+++ b/tests/test_repository.py
@@ -89,7 +89,14 @@ def test_make_user_agent_string(default_repo):
     assert "User-Agent" in default_repo.session.headers
 
     user_agent = default_repo.session.headers["User-Agent"]
-    packages = ("twine/", "requests/", "requests-toolbelt/", "pkginfo/", "setuptools/")
+    packages = (
+        "twine/",
+        "requests/",
+        "requests-toolbelt/",
+        "pkginfo/",
+        "importlib_metadata/",
+        "packaging/",
+    )
     assert all(p in user_agent for p in packages)
 
 
diff --git a/twine/_installed.py b/twine/_installed.py
deleted file mode 100644
index d2dba83b..00000000
--- a/twine/_installed.py
+++ /dev/null
@@ -1,60 +0,0 @@
-# Copyright 2013 Tres Seaver
-# Copyright 2015 Ian Cordasco
-# This code was originally licensed under the Python Software Foudation
-# License by Tres Seaver. In order to facilitate finding the metadata of
-# installed packages, part of the most current implementation of the
-# pkginfo.Installed class is reproduced here with bug fixes from
-# https://bugs.launchpad.net/pkginfo/+bug/1437570.
-import glob
-import os
-import sys
-import warnings
-from typing import Optional
-
-import pkginfo
-
-
-class Installed(pkginfo.Installed):
-    def read(self) -> Optional[str]:
-        opj = os.path.join
-        if self.package is not None:
-            package = self.package.__package__
-            if package is None:
-                package = self.package.__name__
-            egg_pattern = "%s*.egg-info" % package
-            dist_pattern = "%s*.dist-info" % package
-            file: Optional[str] = getattr(self.package, "__file__", None)
-            if file is not None:
-                candidates = []
-
-                def _add_candidate(where: str) -> None:
-                    candidates.extend(glob.glob(where))
-
-                for entry in sys.path:
-                    if file.startswith(entry):
-                        _add_candidate(opj(entry, "METADATA"))  # egg?
-                        _add_candidate(opj(entry, "EGG-INFO"))  # egg?
-                        # dist-installed?
-                        _add_candidate(opj(entry, egg_pattern))
-                        _add_candidate(opj(entry, dist_pattern))
-                dir, name = os.path.split(self.package.__file__)
-                _add_candidate(opj(dir, egg_pattern))
-                _add_candidate(opj(dir, dist_pattern))
-                _add_candidate(opj(dir, "..", egg_pattern))
-                _add_candidate(opj(dir, "..", dist_pattern))
-
-                for candidate in candidates:
-                    if os.path.isdir(candidate):
-                        path = opj(candidate, "PKG-INFO")
-                        if not os.path.exists(path):
-                            path = opj(candidate, "METADATA")
-                    else:
-                        path = candidate
-                    if os.path.exists(path):
-                        with open(path) as f:
-                            return f.read()
-
-        warnings.warn(
-            "No PKG-INFO or METADATA found for package: %s" % self.package_name
-        )
-        return None
diff --git a/twine/cli.py b/twine/cli.py
index e0dc0fc1..cf3efdf2 100644
--- a/twine/cli.py
+++ b/twine/cli.py
@@ -14,27 +14,24 @@
 import argparse
 from typing import Any, List, Tuple
 
-import pkginfo
-import requests
-import requests_toolbelt
-import setuptools
-import tqdm
 from importlib_metadata import entry_points
+from importlib_metadata import version
 
 import twine
-from twine import _installed
 
 args = argparse.Namespace()
 
 
 def list_dependencies_and_versions() -> List[Tuple[str, str]]:
-    return [
-        ("pkginfo", _installed.Installed(pkginfo).version),
-        ("requests", requests.__version__),
-        ("setuptools", setuptools.__version__),
-        ("requests-toolbelt", requests_toolbelt.__version__),
-        ("tqdm", tqdm.__version__),
-    ]
+    deps = (
+        "importlib_metadata",
+        "packaging",
+        "pkginfo",
+        "requests",
+        "requests-toolbelt",
+        "tqdm",
+    )
+    return [(dep, version(dep)) for dep in deps]  # type: ignore[no-untyped-call] # python/importlib_metadata#288  # noqa: E501
 
 
 def dep_versions() -> str:
diff --git a/twine/package.py b/twine/package.py
index 045ad81d..0b68bc9c 100644
--- a/twine/package.py
+++ b/twine/package.py
@@ -17,7 +17,8 @@
 import subprocess
 from typing import Dict, NamedTuple, Optional, Sequence, Tuple, Union
 
-import pkg_resources
+import importlib_metadata
+import packaging.utils
 import pkginfo
 
 from twine import exceptions
@@ -58,7 +59,7 @@ def __init__(
         self.metadata = metadata
         self.python_version = python_version
         self.filetype = filetype
-        self.safe_name = pkg_resources.safe_name(metadata.name)
+        self.safe_name = packaging.utils.canonicalize_name(metadata.name)
         self.signed_filename = self.filename + ".asc"
         self.signed_basefilename = self.basefilename + ".asc"
         self.gpg_signature: Optional[Tuple[str, bytes]] = None
@@ -99,8 +100,10 @@ def from_filename(cls, filename: str, comment: Optional[str]) -> "PackageFile":
 
         py_version: Optional[str]
         if dtype == "bdist_egg":
-            pkgd = pkg_resources.Distribution.from_filename(filename)
-            py_version = pkgd.py_version
+            (dist,) = importlib_metadata.Distribution.discover(  # type: ignore[no-untyped-call] # python/importlib_metadata#288  # noqa: E501
+                path=[filename]
+            )
+            py_version = dist.metadata["Version"]
         elif dtype == "bdist_wheel":
             py_version = meta.py_version
         elif dtype == "bdist_wininst":