diff --git a/doc/source/whatsnew/v0.24.0.txt b/doc/source/whatsnew/v0.24.0.txt
index b19003e1c1284..4084514885aa9 100644
--- a/doc/source/whatsnew/v0.24.0.txt
+++ b/doc/source/whatsnew/v0.24.0.txt
@@ -1150,6 +1150,7 @@ Timezones
 - Bug in :meth:`DatetimeIndex.unique` that did not re-localize tz-aware dates correctly (:issue:`21737`)
 - Bug when indexing a :class:`Series` with a DST transition (:issue:`21846`)
 - Bug in :meth:`DataFrame.resample` and :meth:`Series.resample` where an ``AmbiguousTimeError`` or ``NonExistentTimeError`` would raise if a timezone aware timeseries ended on a DST transition (:issue:`19375`, :issue:`10117`)
+- Bug in :meth:`DataFrame.drop` and :meth:`Series.drop` when specifying a tz-aware Timestamp key to drop from a :class:`DatetimeIndex` with a DST transition (:issue:`21761`)
 
 Offsets
 ^^^^^^^
diff --git a/pandas/tests/test_multilevel.py b/pandas/tests/test_multilevel.py
index 2022340926cca..9829c04ea108f 100644
--- a/pandas/tests/test_multilevel.py
+++ b/pandas/tests/test_multilevel.py
@@ -1931,6 +1931,19 @@ def test_drop_level_nonunique_datetime(self):
         expected = df.loc[idx != 4]
         tm.assert_frame_equal(result, expected)
 
+    @pytest.mark.parametrize('box', [Series, DataFrame])
+    def test_drop_tz_aware_timestamp_across_dst(self, box):
+        # GH 21761
+        start = Timestamp('2017-10-29', tz='Europe/Berlin')
+        end = Timestamp('2017-10-29 04:00:00', tz='Europe/Berlin')
+        index = pd.date_range(start, end, freq='15min')
+        data = box(data=[1] * len(index), index=index)
+        result = data.drop(start)
+        expected_start = Timestamp('2017-10-29 00:15:00', tz='Europe/Berlin')
+        expected_idx = pd.date_range(expected_start, end, freq='15min')
+        expected = box(data=[1] * len(expected_idx), index=expected_idx)
+        tm.assert_equal(result, expected)
+
     def test_drop_preserve_names(self):
         index = MultiIndex.from_arrays([[0, 0, 0, 1, 1, 1],
                                         [1, 2, 3, 1, 2, 3]],