diff --git a/doc/source/whatsnew/v2.0.0.rst b/doc/source/whatsnew/v2.0.0.rst
index 8a628dbce3ca7..a10e99c13e548 100644
--- a/doc/source/whatsnew/v2.0.0.rst
+++ b/doc/source/whatsnew/v2.0.0.rst
@@ -227,6 +227,7 @@ Removal of prior version deprecations/changes
 - Removed ``pandas.SparseArray`` in favor of :class:`arrays.SparseArray` (:issue:`30642`)
 - Removed ``pandas.SparseSeries`` and ``pandas.SparseDataFrame`` (:issue:`30642`)
 - Enforced disallowing a string column label into ``times`` in :meth:`DataFrame.ewm` (:issue:`43265`)
+- Enforced disallowing a tuple of column labels into :meth:`.DataFrameGroupBy.__getitem__` (:issue:`30546`)
 - Removed setting Categorical._codes directly (:issue:`41429`)
 - Enforced :meth:`Rolling.count` with ``min_periods=None`` to default to the size of the window (:issue:`31302`)
 - Enforced the ``display.max_colwidth`` option to not accept negative integers (:issue:`31569`)
diff --git a/pandas/core/groupby/generic.py b/pandas/core/groupby/generic.py
index 109227633cfdd..4c06ee60d3f6a 100644
--- a/pandas/core/groupby/generic.py
+++ b/pandas/core/groupby/generic.py
@@ -1595,12 +1595,10 @@ def __getitem__(self, key) -> DataFrameGroupBy | SeriesGroupBy:
         # per GH 23566
         if isinstance(key, tuple) and len(key) > 1:
             # if len == 1, then it becomes a SeriesGroupBy and this is actually
-            # valid syntax, so don't raise warning
-            warnings.warn(
-                "Indexing with multiple keys (implicitly converted to a tuple "
-                "of keys) will be deprecated, use a list instead.",
-                FutureWarning,
-                stacklevel=find_stack_level(),
+            # valid syntax, so don't raise
+            raise ValueError(
+                "Cannot subset columns with a tuple with more than one element. "
+                "Use a list instead."
             )
         return super().__getitem__(key)
 
diff --git a/pandas/tests/groupby/test_grouping.py b/pandas/tests/groupby/test_grouping.py
index 728575a80f32f..1c8b8e3d33ecf 100644
--- a/pandas/tests/groupby/test_grouping.py
+++ b/pandas/tests/groupby/test_grouping.py
@@ -102,13 +102,13 @@ def test_getitem_numeric_column_names(self):
         tm.assert_frame_equal(result, expected)
         tm.assert_frame_equal(result2, expected)
 
-        # per GH 23566 this should raise a FutureWarning
-        with tm.assert_produces_warning(FutureWarning):
+        # per GH 23566 enforced deprecation raises a ValueError
+        with pytest.raises(ValueError, match="Cannot subset columns with a tuple"):
             df.groupby(0)[2, 4].mean()
 
-    def test_getitem_single_list_of_columns(self, df):
-        # per GH 23566 this should raise a FutureWarning
-        with tm.assert_produces_warning(FutureWarning):
+    def test_getitem_single_tuple_of_columns_raises(self, df):
+        # per GH 23566 enforced deprecation raises a ValueError
+        with pytest.raises(ValueError, match="Cannot subset columns with a tuple"):
             df.groupby("A")["C", "D"].mean()
 
     def test_getitem_single_column(self):