diff --git a/doc/source/whatsnew/v2.2.0.rst b/doc/source/whatsnew/v2.2.0.rst
index d8b63a6d1395d..7384c512f180b 100644
--- a/doc/source/whatsnew/v2.2.0.rst
+++ b/doc/source/whatsnew/v2.2.0.rst
@@ -92,6 +92,7 @@ Other API changes
 
 Deprecations
 ~~~~~~~~~~~~
+- Deprecated allowing non-keyword arguments in :meth:`DataFrame.to_clipboard`. (:issue:`54229`)
 - Deprecated allowing non-keyword arguments in :meth:`DataFrame.to_csv` except ``path_or_buf``. (:issue:`54229`)
 - Deprecated allowing non-keyword arguments in :meth:`DataFrame.to_hdf` except ``path_or_buf``. (:issue:`54229`)
 - Deprecated allowing non-keyword arguments in :meth:`DataFrame.to_html` except ``buf``. (:issue:`54229`)
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index cf60717011222..cc68aa3db6908 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -3098,6 +3098,9 @@ def to_pickle(
         )
 
     @final
+    @deprecate_nonkeyword_arguments(
+        version="3.0", allowed_args=["self"], name="to_clipboard"
+    )
     def to_clipboard(
         self, excel: bool_t = True, sep: str | None = None, **kwargs
     ) -> None:
diff --git a/pandas/tests/io/test_clipboard.py b/pandas/tests/io/test_clipboard.py
index 4b3c82ad3f083..10e0467c5d74d 100644
--- a/pandas/tests/io/test_clipboard.py
+++ b/pandas/tests/io/test_clipboard.py
@@ -471,3 +471,13 @@ def test_invalid_dtype_backend(self):
         )
         with pytest.raises(ValueError, match=msg):
             read_clipboard(dtype_backend="numpy")
+
+    def test_to_clipboard_pos_args_deprecation(self):
+        # GH-54229
+        df = DataFrame({"a": [1, 2, 3]})
+        msg = (
+            r"Starting with pandas version 3.0 all arguments of to_clipboard "
+            r"will be keyword-only."
+        )
+        with tm.assert_produces_warning(FutureWarning, match=msg):
+            df.to_clipboard(True, None)