diff --git a/gnu/packages/aux-files/python/sitecustomize-fixed.py b/gnu/packages/aux-files/python/sitecustomize-fixed.py
new file mode 100644
index 0000000000..82ea91104d
--- /dev/null
+++ b/gnu/packages/aux-files/python/sitecustomize-fixed.py
@@ -0,0 +1,65 @@
+# -*- coding: utf-8 -*-
+# GNU Guix --- Functional package management for GNU
+# Copyright © 2021 Maxim Cournoyer <maxim.cournoyer@gmail.com>
+#
+# This file is part of GNU Guix.
+#
+# GNU Guix is free software; you can redistribute it and/or modify it
+# under the terms of the GNU General Public License as published by
+# the Free Software Foundation; either version 3 of the License, or (at
+# your option) any later version.
+#
+# GNU Guix is distributed in the hope that it will be useful, but
+# WITHOUT ANY WARRANTY; without even the implied warranty of
+# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
+# GNU General Public License for more details.
+#
+# You should have received a copy of the GNU General Public License
+# along with GNU Guix.  If not, see <http://www.gnu.org/licenses/>.
+
+import os
+import site
+import sys
+
+# Commentary:
+#
+# Site-specific customization for Guix.
+#
+# The program below honors the GUIX_PYTHONPATH environment variable to
+# discover Python packages.  File names appearing in this variable that match
+# a predefined versioned installation prefix are added to the sys.path.  To be
+# considered, a Python package must be installed under the
+# 'lib/pythonX.Y/site-packages' directory, where X and Y are the major and
+# minor version numbers of the Python interpreter.
+#
+# Code:
+
+major_minor = '{}.{}'.format(*sys.version_info)
+site_packages_prefix = os.path.join(
+    'lib', 'python' + major_minor, 'site-packages')
+python_site = os.path.normpath(os.path.join(sys.prefix, site_packages_prefix))
+
+try:
+    all_sites_raw = os.environ['GUIX_PYTHONPATH'].split(os.path.pathsep)
+except KeyError:
+    all_sites_raw = []
+# Normalize paths, otherwise a trailing slash would cause it to not match.
+all_sites_norm = [os.path.normpath(p) for p in all_sites_raw]
+matching_sites = [p for p in all_sites_norm
+                  if p.endswith(site_packages_prefix)]
+
+if matching_sites:
+    # Deduplicate the entries, append them to sys.path, and handle any
+    # .pth files they contain.
+    for s in matching_sites:
+        site.addsitedir(s)
+
+    # Move the entries that were appended to sys.path in front of
+    # Python's own site-packages directory.  This enables Guix
+    # packages to override Python's bundled packages, such as 'pip'.
+    python_site_index = sys.path.index(python_site)
+    new_site_start_index = sys.path.index(matching_sites[0])
+    if python_site_index < new_site_start_index:
+        sys.path = (sys.path[:python_site_index]
+                    + sys.path[new_site_start_index:]
+                    + sys.path[python_site_index:new_site_start_index])
diff --git a/gnu/packages/python.scm b/gnu/packages/python.scm
index 51d5f598d7..3cc3c08360 100644
--- a/gnu/packages/python.scm
+++ b/gnu/packages/python.scm
@@ -414,7 +414,16 @@ (define-public python-2.7
 packages; exception-based error handling; and very high level dynamic
 data types.")
     (properties '((cpe-name . "python")))
-    (license license:psfl)))
+    (license license:psfl)
+    (replacement python-2.7-fixed)))
+
+(define-public python-2.7-fixed
+  (package
+    (inherit python-2.7)
+    (native-inputs
+     (modify-inputs (package-native-inputs python-2.7)
+       (replace "sitecustomize.py"
+         (local-file (search-auxiliary-file "python/sitecustomize-fixed.py")))))))
 
 ;; Current 2.x version.
 (define-public python-2 python-2.7)
@@ -594,7 +603,16 @@ (define-public python-3.10
            ;; Python 3.9.
            (search-path-specification
             (variable "PYTHONTZPATH")
-            (files (list "share/zoneinfo")))))))
+            (files (list "share/zoneinfo")))))
+    (replacement python-3.10-fixed)))
+
+(define-public python-3.10-fixed
+  (package
+    (inherit python-3.10)
+    (native-inputs
+     (modify-inputs (package-native-inputs python-3.10)
+       (replace "sitecustomize.py"
+         (local-file (search-auxiliary-file "python/sitecustomize-fixed.py")))))))
 
 ;; Current 3.x version.
 (define-public python-3 python-3.10)
