diff --git a/.ci/scripts/auditwheel_wrapper.py b/.ci/scripts/auditwheel_wrapper.py
new file mode 100755
index 000000000..c744644c2
--- /dev/null
+++ b/.ci/scripts/auditwheel_wrapper.py
@@ -0,0 +1,132 @@
+#!/usr/bin/env python
+# Copyright 2022 The Matrix.org Foundation C.I.C.
+#
+# Licensed under the Apache License, Version 2.0 (the "License");
+# you may not use this file except in compliance with the License.
+# You may obtain a copy of the License at
+#
+#     http://www.apache.org/licenses/LICENSE-2.0
+#
+# Unless required by applicable law or agreed to in writing, software
+# distributed under the License is distributed on an "AS IS" BASIS,
+# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+# See the License for the specific language governing permissions and
+# limitations under the License.
+
+# Wraps `auditwheel repair` to first check if we're repairing a potentially abi3
+# compatible wheel, if so rename the wheel before repairing it.
+
+import argparse
+import os
+import subprocess
+from typing import Optional
+from zipfile import ZipFile
+
+from packaging.tags import Tag
+from packaging.utils import parse_wheel_filename
+from packaging.version import Version
+
+
+def check_is_abi3_compatible(wheel_file: str) -> None:
+    """Check the contents of the built wheel for any `.so` files that are *not*
+    abi3 compatible.
+    """
+
+    with ZipFile(wheel_file, "r") as wheel:
+        for file in wheel.namelist():
+            if not file.endswith(".so"):
+                continue
+
+            if not file.endswith(".abi3.so"):
+                raise Exception(f"Found non-abi3 lib: {file}")
+
+
+def cpython(wheel_file: str, name: str, version: Version, tag: Tag) -> str:
+    """Replaces the cpython wheel file with a ABI3 compatible wheel"""
+
+    if tag.abi == "abi3":
+        # Nothing to do.
+        return wheel_file
+
+    check_is_abi3_compatible(wheel_file)
+
+    abi3_tag = Tag(tag.interpreter, "abi3", tag.platform)
+
+    dirname = os.path.dirname(wheel_file)
+    new_wheel_file = os.path.join(
+        dirname,
+        f"{name}-{version}-{abi3_tag}.whl",
+    )
+
+    os.rename(wheel_file, new_wheel_file)
+
+    print("Renamed wheel to", new_wheel_file)
+
+    return new_wheel_file
+
+
+def main(wheel_file: str, dest_dir: str, archs: Optional[str]) -> None:
+    """Entry point"""
+
+    # Parse the wheel file name into its parts. Note that `parse_wheel_filename`
+    # normalizes the package name (i.e. it converts matrix_synapse ->
+    # matrix-synapse), which is not what we want.
+    _, version, build, tags = parse_wheel_filename(os.path.basename(wheel_file))
+    name = os.path.basename(wheel_file).split("-")[0]
+
+    if len(tags) != 1:
+        # We expect only a wheel file with only a single tag
+        raise Exception(f"Unexpectedly found multiple tags: {tags}")
+
+    tag = next(iter(tags))
+
+    if build:
+        # We don't use build tags in Synapse
+        raise Exception(f"Unexpected build tag: {build}")
+
+    # If the wheel is for cpython then convert it into an abi3 wheel.
+    if tag.interpreter.startswith("cp"):
+        wheel_file = cpython(wheel_file, name, version, tag)
+
+    # Finally, repair the wheel.
+    if archs is not None:
+        # If we are given archs then we are on macos and need to use
+        # `delocate-listdeps`.
+        subprocess.run(["delocate-listdeps", wheel_file], check=True)
+        subprocess.run(
+            ["delocate-wheel" "--require-archs", archs, "-w", dest_dir, wheel_file],
+            check=True,
+        )
+    else:
+        subprocess.run(["auditwheel", "repair", "-w", dest_dir, wheel_file], check=True)
+
+
+if __name__ == "__main__":
+    parser = argparse.ArgumentParser(description="Tag wheel as abi3 and repair it.")
+
+    parser.add_argument(
+        "--wheel-dir",
+        "-w",
+        metavar="WHEEL_DIR",
+        help="Directory to store delocated wheels",
+        required=True,
+    )
+
+    parser.add_argument(
+        "--require-archs",
+        metavar="archs",
+        default=None,
+    )
+
+    parser.add_argument(
+        "wheel_file",
+        metavar="WHEEL_FILE",
+    )
+
+    args = parser.parse_args()
+
+    wheel_file = args.wheel_file
+    wheel_dir = args.wheel_dir
+    archs = args.require_archs
+
+    main(wheel_file, wheel_dir, archs)
diff --git a/changelog.d/14253.misc b/changelog.d/14253.misc
new file mode 100644
index 000000000..c1382ddaf
--- /dev/null
+++ b/changelog.d/14253.misc
@@ -0,0 +1 @@
+Build ABI3 wheels for cpython.
diff --git a/pyproject.toml b/pyproject.toml
index 6ebac41ed..78011be49 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -330,3 +330,12 @@ environment= { PATH = "$PATH:$HOME/.cargo/bin" }
 before-build = "rm -rf {project}/build"
 build-frontend = "build"
 test-command = "python -c 'from synapse.synapse_rust import sum_as_string; print(sum_as_string(1, 2))'"
+
+
+[tool.cibuildwheel.linux]
+# Wrap the repair command to correctly rename the built cpython wheels as ABI3.
+repair-wheel-command = "./.ci/scripts/auditwheel_wrapper.py -w {dest_dir} {wheel}"
+
+[tool.cibuildwheel.macos]
+# Wrap the repair command to correctly rename the built cpython wheels as ABI3.
+repair-wheel-command = "./.ci/scripts/auditwheel_wrapper.py --require-archs {delocate_archs} -w {dest_dir} {wheel}"