diff --git a/tests/test_package.py b/tests/test_package.py
index ee666130..1b36c665 100644
--- a/tests/test_package.py
+++ b/tests/test_package.py
@@ -467,3 +467,34 @@ def test_malformed_from_file(monkeypatch):
 def test_package_from_egg():
     filename = "tests/fixtures/twine-3.3.0-py3.9.egg"
     package_file.PackageFile.from_filename(filename, comment=None)
+
+
+@pytest.mark.parametrize(
+    "read_data, filtered",
+    [
+        pytest.param(
+            "Metadata-Version: 2.1\n"
+            "Name: test-package\n"
+            "Version: 1.0.0\n"
+            "License-File: LICENSE\n",
+            True,
+            id="invalid License-File",
+        ),
+        pytest.param(
+            "Metadata-Version: 2.4\n"
+            "Name: test-package\n"
+            "Version: 1.0.0\n"
+            "License-File: LICENSE\n",
+            False,
+            id="valid License-File",
+        ),
+    ],
+)
+def test_setuptools_license_file(read_data, filtered, monkeypatch):
+    """Drop License-File metadata entries if Metadata-Version is less than 2.4."""
+    monkeypatch.setattr(package_file.wheel.Wheel, "read", lambda _: read_data)
+    filename = "tests/fixtures/twine-1.5.0-py2.py3-none-any.whl"
+
+    package = package_file.PackageFile.from_filename(filename, comment=None)
+    meta = package.metadata_dictionary()
+    assert filtered != ("license_files" in meta)
diff --git a/twine/package.py b/twine/package.py
index 26da5e54..509a2d45 100644
--- a/twine/package.py
+++ b/twine/package.py
@@ -21,6 +21,7 @@
 from typing import Any, Dict, List, NamedTuple, Optional, Tuple
 
 from packaging import metadata
+from packaging import version
 from rich import print
 
 from twine import bdist
@@ -142,6 +143,16 @@ def from_filename(cls, filename: str, comment: Optional[str]) -> "PackageFile":
                     )
                 )
             )
+        # setuptools emits License-File metadata fields while declaring
+        # Metadata-Version 2.1. This is invalid because the metadata
+        # specification does not allow to add arbitrary fields, and because
+        # the semantic implemented by setuptools is different than the one
+        # described in PEP 639. However, rejecting these packages would be
+        # too disruptive. Drop License-File metadata entries from the data
+        # sent to the package index if the declared metadata version is less
+        # than 2.4.
+        if version.Version(meta.get("metadata_version", "0")) < version.Version("2.4"):
+            meta.pop("license_files", None)
         try:
             metadata.Metadata.from_raw(meta)
         except metadata.ExceptionGroup as group: