diff --git a/doc/source/whatsnew/v2.1.0.rst b/doc/source/whatsnew/v2.1.0.rst
index 56284ba9a9ebf..5c901e1e54d63 100644
--- a/doc/source/whatsnew/v2.1.0.rst
+++ b/doc/source/whatsnew/v2.1.0.rst
@@ -370,6 +370,7 @@ Missing
 MultiIndex
 ^^^^^^^^^^
 - Bug in :meth:`DataFrame.__getitem__` not preserving dtypes for :class:`MultiIndex` partial keys (:issue:`51895`)
+- Bug in :meth:`DatetimeIndexResamplerGroupby.agg({})`, where the aggregatio function wouldn't work if :class:`DatetimeIndexResamplerGroupby` was created from :class:`Groupby` w. ``as_index=False`` (:issue:`52819`)
 - Bug in :meth:`MultiIndex.set_levels` not preserving dtypes for :class:`Categorical` (:issue:`52125`)
 
 I/O
diff --git a/pandas/core/resample.py b/pandas/core/resample.py
index f8adb2332609b..836461c5a644e 100644
--- a/pandas/core/resample.py
+++ b/pandas/core/resample.py
@@ -1,10 +1,12 @@
 from __future__ import annotations
 
+from contextlib import nullcontext
 import copy
 from textwrap import dedent
 from typing import (
     TYPE_CHECKING,
     Callable,
+    ContextManager,
     Hashable,
     Literal,
     cast,
@@ -327,7 +329,13 @@ def pipe(
         axis="",
     )
     def aggregate(self, func=None, *args, **kwargs):
-        result = ResamplerWindowApply(self, func, args=args, kwargs=kwargs).agg()
+        context_manager: ContextManager
+        if isinstance(self, DatetimeIndexResamplerGroupby):
+            context_manager = com.temp_setattr(self._groupby, "as_index", True)
+        else:
+            context_manager = nullcontext()
+        with context_manager:
+            result = ResamplerWindowApply(self, func, args=args, kwargs=kwargs).agg()
         if result is None:
             how = func
             result = self._groupby_and_aggregate(how, *args, **kwargs)
diff --git a/pandas/tests/resample/test_resampler_grouper.py b/pandas/tests/resample/test_resampler_grouper.py
index 1682edb42915d..1c14ad8e8f8b3 100644
--- a/pandas/tests/resample/test_resampler_grouper.py
+++ b/pandas/tests/resample/test_resampler_grouper.py
@@ -659,3 +659,29 @@ def test_groupby_resample_on_index_with_list_of_keys_missing_column():
     )
     with pytest.raises(KeyError, match="Columns not found"):
         df.groupby("group").resample("2D")[["val_not_in_dataframe"]].mean()
+
+
+def test_groupby_resample_agg_dict_works_for_as_index_false():
+    # GH 52397
+    expected = (
+        DataFrame(
+            {"a": np.repeat([0, 1, 2, 3, 4], 2), "b": range(50, 60)},
+            index=date_range(start=Timestamp.now(), freq="1min", periods=10),
+        )
+        .groupby("a", as_index=True)
+        .resample("2min")
+        .min()
+    )
+    expected.drop(columns=["a"], inplace=True)
+
+    result = (
+        DataFrame(
+            {"a": np.repeat([0, 1, 2, 3, 4], 2), "b": range(50, 60)},
+            index=date_range(start=Timestamp.now(), freq="1min", periods=10),
+        )
+        .groupby("a", as_index=False)
+        .resample("2min")
+        .agg({"b": "min"})
+    )
+
+    tm.assert_frame_equal(expected, result)