diff --git a/src/pip/_internal/locations/__init__.py b/src/pip/_internal/locations/__init__.py
index aee98ca51d0..be18f21bb58 100644
--- a/src/pip/_internal/locations/__init__.py
+++ b/src/pip/_internal/locations/__init__.py
@@ -8,6 +8,7 @@
 
 from pip._internal.models.scheme import SCHEME_KEYS, Scheme
 from pip._internal.utils.compat import WINDOWS
+from pip._internal.utils.deprecation import deprecated
 
 from . import _distutils, _sysconfig
 from .base import (
@@ -99,9 +100,7 @@ def _default_base(*, user: bool) -> str:
 
 
 @functools.lru_cache(maxsize=None)
-def _warn_if_mismatch(old: pathlib.Path, new: pathlib.Path, *, key: str) -> bool:
-    if old == new:
-        return False
+def _warn_mismatched(old: pathlib.Path, new: pathlib.Path, *, key: str) -> None:
     issue_url = "https://github.com/pypa/pip/issues/10151"
     message = (
         "Value for %s does not match. Please report this to <%s>"
@@ -109,6 +108,12 @@ def _warn_if_mismatch(old: pathlib.Path, new: pathlib.Path, *, key: str) -> bool
         "\nsysconfig: %s"
     )
     logger.log(_MISMATCH_LEVEL, message, key, issue_url, old, new)
+
+
+def _warn_if_mismatch(old: pathlib.Path, new: pathlib.Path, *, key: str) -> bool:
+    if old == new:
+        return False
+    _warn_mismatched(old, new, key=key)
     return True
 
 
@@ -157,12 +162,15 @@ def get_scheme(
     )
 
     base = prefix or home or _default_base(user=user)
-    warned = []
+    warning_contexts = []
     for k in SCHEME_KEYS:
         # Extra join because distutils can return relative paths.
         old_v = pathlib.Path(base, getattr(old, k))
         new_v = pathlib.Path(getattr(new, k))
 
+        if old_v == new_v:
+            continue
+
         # distutils incorrectly put PyPy packages under ``site-packages/python``
         # in the ``posix_home`` scheme, but PyPy devs said they expect the
         # directory name to be ``pypy`` instead. So we treat this as a bug fix
@@ -221,10 +229,38 @@ def get_scheme(
         if skip_sysconfig_abiflag_bug:
             continue
 
-        warned.append(_warn_if_mismatch(old_v, new_v, key=f"scheme.{k}"))
+        warning_contexts.append((old_v, new_v, f"scheme.{k}"))
 
-    if any(warned):
-        _log_context(user=user, home=home, root=root, prefix=prefix)
+    if not warning_contexts:
+        return old
+
+    # Check if this path mismatch is caused by distutils config files. Those
+    # files will no longer work once we switch to sysconfig, so this raises a
+    # deprecation message for them.
+    default_old = _distutils.distutils_scheme(
+        dist_name,
+        user,
+        home,
+        root,
+        isolated,
+        prefix,
+        ignore_config_files=True,
+    )
+    if any(default_old[k] != getattr(old, k) for k in SCHEME_KEYS):
+        deprecated(
+            "Configuring installation scheme with distutils config files "
+            "is deprecated and will no longer work in the near future. If you "
+            "are using a Homebrew or Linuxbrew Python, please see discussion "
+            "at https://github.com/Homebrew/homebrew-core/issues/76621",
+            replacement=None,
+            gone_in=None,
+        )
+        return old
+
+    # Post warnings about this mismatch so user can report them back.
+    for old_v, new_v, key in warning_contexts:
+        _warn_mismatched(old_v, new_v, key=key)
+    _log_context(user=user, home=home, root=root, prefix=prefix)
 
     return old
 
diff --git a/src/pip/_internal/locations/_distutils.py b/src/pip/_internal/locations/_distutils.py
index 38742d1ddb6..6d7c09dd0fb 100644
--- a/src/pip/_internal/locations/_distutils.py
+++ b/src/pip/_internal/locations/_distutils.py
@@ -21,13 +21,15 @@
 logger = logging.getLogger(__name__)
 
 
-def _distutils_scheme(
+def distutils_scheme(
     dist_name: str,
     user: bool = False,
     home: str = None,
     root: str = None,
     isolated: bool = False,
     prefix: str = None,
+    *,
+    ignore_config_files: bool = False,
 ) -> Dict[str, str]:
     """
     Return a distutils install scheme
@@ -39,15 +41,16 @@ def _distutils_scheme(
         dist_args["script_args"] = ["--no-user-cfg"]
 
     d = Distribution(dist_args)
-    try:
-        d.parse_config_files()
-    except UnicodeDecodeError:
-        # Typeshed does not include find_config_files() for some reason.
-        paths = d.find_config_files()  # type: ignore
-        logger.warning(
-            "Ignore distutils configs in %s due to encoding errors.",
-            ", ".join(os.path.basename(p) for p in paths),
-        )
+    if not ignore_config_files:
+        try:
+            d.parse_config_files()
+        except UnicodeDecodeError:
+            # Typeshed does not include find_config_files() for some reason.
+            paths = d.find_config_files()  # type: ignore
+            logger.warning(
+                "Ignore distutils configs in %s due to encoding errors.",
+                ", ".join(os.path.basename(p) for p in paths),
+            )
     obj: Optional[DistutilsCommand] = None
     obj = d.get_command_obj("install", create=True)
     assert obj is not None
@@ -121,7 +124,7 @@ def get_scheme(
     :param prefix: indicates to use the "prefix" scheme and provides the
         base directory for the same
     """
-    scheme = _distutils_scheme(dist_name, user, home, root, isolated, prefix)
+    scheme = distutils_scheme(dist_name, user, home, root, isolated, prefix)
     return Scheme(
         platlib=scheme["platlib"],
         purelib=scheme["purelib"],