diff --git a/Lib/sysconfig/__init__.py b/Lib/sysconfig/__init__.py
index ec3b638f007..67a071963d8 100644
--- a/Lib/sysconfig/__init__.py
+++ b/Lib/sysconfig/__init__.py
@@ -353,7 +353,8 @@ def _init_posix(vars):
     else:
         _temp = __import__(name, globals(), locals(), ['build_time_vars'], 0)
     build_time_vars = _temp.build_time_vars
-    vars.update(build_time_vars)
+    # GH-126920: Make sure we don't overwrite any of the keys already set
+    vars.update(build_time_vars | vars)
 
 def _init_non_posix(vars):
     """Initialize the module as appropriate for NT"""
diff --git a/Lib/test/test_sysconfig.py b/Lib/test/test_sysconfig.py
index 4f9541b6a0b..c7acfe728bb 100644
--- a/Lib/test/test_sysconfig.py
+++ b/Lib/test/test_sysconfig.py
@@ -656,6 +656,38 @@ def test_paths_depend_on_site_initialization(self):
 
         self.assertNotEqual(site_paths, no_site_paths)
 
+    @unittest.skipIf(sys.platform == 'wasi', 'venv is unsupported on WASI')
+    def test_makefile_overwrites_config_vars(self):
+        script = textwrap.dedent("""
+            import sys, sysconfig
+
+            data = {
+                'prefix': sys.prefix,
+                'exec_prefix': sys.exec_prefix,
+                'base_prefix': sys.base_prefix,
+                'base_exec_prefix': sys.base_exec_prefix,
+                'config_vars': sysconfig.get_config_vars(),
+            }
+
+            import json
+            print(json.dumps(data, indent=2))
+        """)
+
+        # We need to run the test inside a virtual environment so that
+        # sys.prefix/sys.exec_prefix have a different value from the
+        # prefix/exec_prefix Makefile variables.
+        with self.venv() as venv:
+            data = json.loads(venv.run('-c', script).stdout)
+
+        # We expect sysconfig.get_config_vars to correctly reflect sys.prefix/sys.exec_prefix
+        self.assertEqual(data['prefix'], data['config_vars']['prefix'])
+        self.assertEqual(data['exec_prefix'], data['config_vars']['exec_prefix'])
+        # As a sanity check, just make sure sys.prefix/sys.exec_prefix really
+        # are different from the Makefile values.
+        # sys.base_prefix/sys.base_exec_prefix should reflect the value of the
+        # prefix/exec_prefix Makefile variables, so we use them in the comparison.
+        self.assertNotEqual(data['prefix'], data['base_prefix'])
+        self.assertNotEqual(data['exec_prefix'], data['base_exec_prefix'])
 
 class MakefileTests(unittest.TestCase):
 
diff --git a/Misc/NEWS.d/next/Library/2024-11-17-01-14-59.gh-issue-126920.s8-f_L.rst b/Misc/NEWS.d/next/Library/2024-11-17-01-14-59.gh-issue-126920.s8-f_L.rst
new file mode 100644
index 00000000000..6966aec380f
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2024-11-17-01-14-59.gh-issue-126920.s8-f_L.rst
@@ -0,0 +1,5 @@
+Fix the ``prefix`` and ``exec_prefix`` keys from
+:py:func:`sysconfig.get_config_vars` incorrectly having the same value as
+:py:const:`sys.base_prefix` and :py:const:`sys.base_exec_prefix`,
+respectively, inside virtual environments. They now accurately reflect
+:py:const:`sys.prefix` and :py:const:`sys.exec_prefix`.