diff --git a/Lib/ssl.py b/Lib/ssl.py
index 1d5873726441e4..b037416e2b3fb9 100644
--- a/Lib/ssl.py
+++ b/Lib/ssl.py
@@ -264,6 +264,14 @@ class _TLSMessageType:
 import errno
 import warnings
 
+if not OPENSSL_VERSION_INFO[:2] == _OPENSSL_API_VERSION[:2]:
+    warnings.warn(
+        "Python was compiled against OpenSSL "
+        f"{_OPENSSL_API_VERSION[0]}.{_OPENSSL_API_VERSION[1]}, "
+        "but is using OpenSSL "
+        f"{OPENSSL_VERSION_INFO[0]}.{OPENSSL_VERSION_INFO[1]}. "
+        "OpenSSL does not guarantee compatibility between different major versions.",
+        category=RuntimeWarning, stacklevel=2)
 
 socket_error = OSError  # keep that public name in module namespace
 
diff --git a/Misc/NEWS.d/next/Core and Builtins/2022-12-31-13-27-16.gh-issue-99951.BGyDJT.rst b/Misc/NEWS.d/next/Core and Builtins/2022-12-31-13-27-16.gh-issue-99951.BGyDJT.rst
new file mode 100644
index 00000000000000..c2583e008ac411
--- /dev/null
+++ b/Misc/NEWS.d/next/Core and Builtins/2022-12-31-13-27-16.gh-issue-99951.BGyDJT.rst	
@@ -0,0 +1 @@
+Raises :exc:`RuntimeWarning` when there is an OpenSSL major version mismatch between the version python was compiled against and the version python is currently using.