diff --git a/build-support/common.sh b/build-support/common.sh
index 5beae71b469..0601b0d047d 100644
--- a/build-support/common.sh
+++ b/build-support/common.sh
@@ -69,3 +69,7 @@ function determine_python() {
 function is_macos_arm() {
   [[ $(uname -sm) == "Darwin arm64" ]]
 }
+
+function is_macos_big_sur() {
+  [[ $(uname) == "Darwin" && $(sw_vers -productVersion) = 11\.* ]]
+}
diff --git a/cargo b/cargo
index fe3b4307772..d9cec177ee1 100755
--- a/cargo
+++ b/cargo
@@ -11,6 +11,17 @@ PY="$(determine_python)"
 export PY
 export PYO3_PYTHON="${PY}"
 export PYTHON_SYS_EXECUTABLE="${PY}" # Consumed by the cpython crate.
+if is_macos_big_sur; then
+  # With Big Sur, MacOS changed its versioning scheme from 10.X to 11.X. A pantsbuild.pants
+  # wheel built on Big Sur will declare its platform (in its name) as macosx_11_0. Unfortunately
+  # pip does not yet recognize that as a compatible platform for Big Sur.
+  # Fortunately, Big Sur may also be identified as 10.16, for backwards compatibility with the old
+  # versioning scheme. Setting MACOSX_DEPLOYMENT_TARGET=10.16 when building the wheel will cause
+  # that wheel to declare its platform as macosx_10_16, which pip will then happily install.
+  # However, in order to build the wheel as macosx_10_16 we must also build the native code for
+  # that platform string, hence this setting here.
+  export MACOSX_DEPLOYMENT_TARGET=10.16
+fi
 
 if ! command -v rustup &> /dev/null; then
   die "Please install Rustup and ensure \`rustup\` is on your PATH (usually by adding ~/.cargo/bin). See https://rustup.rs."
diff --git a/pants.toml b/pants.toml
index 49d2ad7c094..4be9bffa03c 100644
--- a/pants.toml
+++ b/pants.toml
@@ -74,6 +74,7 @@ root_patterns = [
 [python-setup]
 experimental_lockfile = "3rdparty/python/lockfiles/user_reqs.txt"
 interpreter_constraints = [">=3.7,<3.10"]
+macos_big_sur_compatibility = true
 
 [docformatter]
 args = ["--wrap-summaries=100", "--wrap-descriptions=100"]
diff --git a/src/python/pants/backend/python/goals/setup_py.py b/src/python/pants/backend/python/goals/setup_py.py
index d07ee4c3418..6d956fbe078 100644
--- a/src/python/pants/backend/python/goals/setup_py.py
+++ b/src/python/pants/backend/python/goals/setup_py.py
@@ -69,6 +69,7 @@
 from pants.util.memo import memoized_property
 from pants.util.meta import frozen_after_init
 from pants.util.ordered_set import FrozenOrderedSet
+from pants.util.osutil import is_macos_big_sur
 from pants.util.strutil import ensure_text
 
 logger = logging.getLogger(__name__)
@@ -410,7 +411,9 @@ async def package_python_dist(
 
 
 @rule
-async def run_setup_py(req: RunSetupPyRequest, setuptools: Setuptools) -> RunSetupPyResult:
+async def run_setup_py(
+    req: RunSetupPyRequest, setuptools: Setuptools, python_setup: PythonSetup
+) -> RunSetupPyResult:
     """Run a setup.py command on a single exported target."""
     # Note that this pex has no entrypoint. We use it to run our generated setup.py, which
     # in turn imports from and invokes setuptools.
@@ -443,12 +446,17 @@ async def run_setup_py(req: RunSetupPyRequest, setuptools: Setuptools) -> RunSet
     setup_script_reldir, setup_script_name = os.path.split(req.chroot.setup_script)
     working_directory = os.path.join(chroot_prefix, setup_script_reldir)
 
+    if python_setup.macos_big_sur_compatibility and is_macos_big_sur():
+        extra_env = {"MACOSX_DEPLOYMENT_TARGET": "10.16"}
+    else:
+        extra_env = {}
     result = await Get(
         ProcessResult,
         VenvPexProcess(
             setuptools_pex,
             argv=(setup_script_name, *req.args),
             input_digest=prefixed_chroot,
+            extra_env=extra_env,
             working_directory=working_directory,
             # setuptools commands that create dists write them to the distdir.
             # TODO: Could there be other useful files to capture?
diff --git a/src/python/pants/python/python_setup.py b/src/python/pants/python/python_setup.py
index bfdafdb37b7..02d36cd97ff 100644
--- a/src/python/pants/python/python_setup.py
+++ b/src/python/pants/python/python_setup.py
@@ -216,6 +216,16 @@ def register_options(cls, register):
             help="Tailor pex_binary() targets for Python entry point files.",
         )
 
+        register(
+            "--macos-big-sur-compatibility",
+            type=bool,
+            default=False,
+            help="If set, and if running on MacOS Big Sur, use macosx_10_16 as the platform "
+            "when building wheels. Otherwise, the default of macosx_11_0 will be used. "
+            "This may be required for pip to be able to install the resulting distribution "
+            "on Big Sur.",
+        )
+
     @property
     def interpreter_constraints(self) -> Tuple[str, ...]:
         return tuple(self.options.interpreter_constraints)
@@ -271,6 +281,10 @@ def tailor_ignore_solitary_init_files(self) -> bool:
     def tailor_pex_binary_targets(self) -> bool:
         return cast(bool, self.options.tailor_pex_binary_targets)
 
+    @property
+    def macos_big_sur_compatibility(self) -> bool:
+        return cast(bool, self.options.macos_big_sur_compatibility)
+
     @property
     def scratch_dir(self):
         return os.path.join(self.options.pants_workdir, *self.options_scope.split("."))
diff --git a/src/python/pants/util/osutil.py b/src/python/pants/util/osutil.py
index 8ba8f6a6295..350953d62f0 100644
--- a/src/python/pants/util/osutil.py
+++ b/src/python/pants/util/osutil.py
@@ -6,6 +6,7 @@
 import errno
 import logging
 import os
+import platform
 import posix
 from functools import reduce
 from typing import Optional
@@ -95,6 +96,10 @@ def get_normalized_arch_name() -> str:
     return normalize_arch_name(get_arch_name())
 
 
+def is_macos_big_sur() -> bool:
+    return hasattr(platform, "mac_ver") and platform.mac_ver()[0].startswith("11.")
+
+
 def _values(aliases: dict[str, set[str]]) -> set[str]:
     return reduce(set.union, aliases.values())