diff --git a/doc/source/whatsnew/v1.2.0.rst b/doc/source/whatsnew/v1.2.0.rst
index e488ca52be8a0..b1e43485cc44e 100644
--- a/doc/source/whatsnew/v1.2.0.rst
+++ b/doc/source/whatsnew/v1.2.0.rst
@@ -233,6 +233,7 @@ Other enhancements
 - :func:`read_csv` supports memory-mapping for compressed files (:issue:`37621`)
 - Improve error reporting for :meth:`DataFrame.merge()` when invalid merge column definitions were given (:issue:`16228`)
 - Improve numerical stability for :meth:`Rolling.skew()`, :meth:`Rolling.kurt()`, :meth:`Expanding.skew()` and :meth:`Expanding.kurt()` through implementation of Kahan summation (:issue:`6929`)
+- Improved error reporting for subsetting columns of a :class:`DataFrameGroupBy` with ``axis=1`` (:issue:`37725`)
 
 .. _whatsnew_120.api_breaking.python:
 
diff --git a/pandas/core/groupby/generic.py b/pandas/core/groupby/generic.py
index d0b58e8abc4ee..6f86819303537 100644
--- a/pandas/core/groupby/generic.py
+++ b/pandas/core/groupby/generic.py
@@ -1530,6 +1530,9 @@ def filter(self, func, dropna=True, *args, **kwargs):
         return self._apply_filter(indices, dropna)
 
     def __getitem__(self, key):
+        if self.axis == 1:
+            # GH 37725
+            raise ValueError("Cannot subset columns when using axis=1")
         # per GH 23566
         if isinstance(key, tuple) and len(key) > 1:
             # if len == 1, then it becomes a SeriesGroupBy and this is actually
diff --git a/pandas/tests/groupby/test_groupby.py b/pandas/tests/groupby/test_groupby.py
index a0c228200e73a..3a4abd58f0d39 100644
--- a/pandas/tests/groupby/test_groupby.py
+++ b/pandas/tests/groupby/test_groupby.py
@@ -2081,7 +2081,6 @@ def test_group_on_two_row_multiindex_returns_one_tuple_key():
 @pytest.mark.parametrize(
     "klass, attr, value",
     [
-        (DataFrame, "axis", 1),
         (DataFrame, "level", "a"),
         (DataFrame, "as_index", False),
         (DataFrame, "sort", False),
@@ -2120,6 +2119,14 @@ def test_subsetting_columns_keeps_attrs(klass, attr, value):
     assert getattr(result, attr) == getattr(expected, attr)
 
 
+def test_subsetting_columns_axis_1():
+    # GH 37725
+    g = DataFrame({"A": [1], "B": [2], "C": [3]}).groupby([0, 0, 1], axis=1)
+    match = "Cannot subset columns when using axis=1"
+    with pytest.raises(ValueError, match=match):
+        g[["A", "B"]].sum()
+
+
 @pytest.mark.parametrize("func", ["sum", "any", "shift"])
 def test_groupby_column_index_name_lost(func):
     # GH: 29764 groupby loses index sometimes