diff --git a/Lib/pdb.py b/Lib/pdb.py
index fc83728fb6dc94..ed13de2f587cd9 100644
--- a/Lib/pdb.py
+++ b/Lib/pdb.py
@@ -2647,6 +2647,16 @@ def set_trace(*, header=None, commands=None):
     just before debugging begins. *commands* is an optional list of
     pdb commands to run when the debugger starts.
     """
+    # gh-138641: Check if we're already in a pdb session.
+    frame = sys._getframe()
+    while frame:
+        if (frame.f_code.co_name == 'interaction'
+            and frame.f_code.co_filename.endswith('pdb.py')):
+            print("Nested breakpoint calls are not supported. "
+                  "Already running in the debugger.", file=sys.stderr)
+            return
+        frame = frame.f_back
+
     if Pdb._last_pdb_instance is not None:
         pdb = Pdb._last_pdb_instance
     else:
@@ -2662,6 +2672,17 @@ async def set_trace_async(*, header=None, commands=None):
     if they enter the debugger with this function. Otherwise it's the same
     as set_trace().
     """
+    # gh-138641: Check if we're already in a pdb session.
+    frame = sys._getframe()
+    while frame:
+        if (frame.f_code.co_name == 'interaction' and
+            frame.f_code.co_filename.endswith('pdb.py')):
+            # We're already in a pdb session, just print a message and return
+            print("Nested breakpoint calls are not supported. "
+                  "Already running in the debugger.", file=sys.stderr)
+            return
+        frame = frame.f_back
+
     if Pdb._last_pdb_instance is not None:
         pdb = Pdb._last_pdb_instance
     else:
diff --git a/Lib/test/test_pdb.py b/Lib/test/test_pdb.py
index 6b74e21ad73d1a..056949325a1399 100644
--- a/Lib/test/test_pdb.py
+++ b/Lib/test/test_pdb.py
@@ -17,14 +17,14 @@
 import zipfile
 
 from asyncio.events import _set_event_loop_policy
-from contextlib import ExitStack, redirect_stdout
+from contextlib import ExitStack, redirect_stdout, redirect_stderr
 from io import StringIO
 from test import support
 from test.support import has_socket_support, os_helper
 from test.support.import_helper import import_module
 from test.support.pty_helper import run_pty, FakeInput
 from test.support.script_helper import kill_python
-from unittest.mock import patch
+from unittest.mock import Mock, patch
 
 SKIP_CORO_TESTS = False
 
@@ -4539,6 +4539,18 @@ def bar():
             ]))
             self.assertIn('break in bar', stdout)
 
+    def test_nested_breakpoint_calls(self):
+        # gh-138641 pdb.set_trace() called when already in the debugger
+        mock_frame = Mock()
+        mock_frame.f_code.co_name = 'interaction'
+        mock_frame.f_code.co_filename = '/path/to/pdb.py'
+        mock_frame.f_back = None
+        captured_stderr = io.StringIO()
+        with redirect_stderr(captured_stderr):
+            with patch('sys._getframe', return_value=mock_frame):
+                pdb.set_trace()
+        stderr_content = captured_stderr.getvalue()
+        self.assertIn("Nested breakpoint calls are not supported", stderr_content)
 
 class ChecklineTests(unittest.TestCase):
     def setUp(self):
diff --git a/Misc/NEWS.d/next/Library/2025-09-08-17-50-33.gh-issue-138641.nBPvKe.rst b/Misc/NEWS.d/next/Library/2025-09-08-17-50-33.gh-issue-138641.nBPvKe.rst
new file mode 100644
index 00000000000000..c0b0a743fe921c
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2025-09-08-17-50-33.gh-issue-138641.nBPvKe.rst
@@ -0,0 +1,2 @@
+Prevent error when calling :func:`breakpoint` inside a :mod:`pdb` debugging session.
+Nested breakpoint calls now display a helpful error message instead of causing error.