diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 3f9749f1f7a99..f410cdff6d3de 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -31,6 +31,7 @@
 from pandas.util._decorators import (
     doc,
 )
+from pandas.util._exceptions import find_stack_level
 
 from pandas.core.dtypes.cast import (
     can_hold_element,
@@ -63,6 +64,7 @@
 )
 
 from pandas.core import algorithms as algos
+from pandas.core.arrays import ExtensionArray
 import pandas.core.common as com
 from pandas.core.construction import (
     array as pd_array,
@@ -926,6 +928,7 @@ def __setitem__(self, key, value) -> None:
                     _chained_assignment_msg, ChainedAssignmentError, stacklevel=2
                 )
 
+        self._maybe_warn_non_casting_setitem(key, value)
         check_dict_or_set_indexers(key)
         if isinstance(key, tuple):
             key = (list(x) if is_iterator(x) else x for x in key)
@@ -941,6 +944,47 @@ def __setitem__(self, key, value) -> None:
         )
         iloc._setitem_with_indexer(indexer, value, self.name)
 
+    @final
+    def _maybe_warn_non_casting_setitem(self, key, value) -> None:
+        # GH#52593 many users got confused by this, so issue a warning
+
+        if (
+            self.ndim == 2
+            and isinstance(key, tuple)
+            and len(key) > 1
+            and isinstance(key[0], slice)
+            and key[0] == slice(None)
+        ):
+            # This is a `df.loc[:, foo] = bar` call
+            if (
+                is_hashable(key[1])
+                and not isinstance(key[1], slice)
+                and not (
+                    isinstance(key[1], tuple)
+                    and any(isinstance(x, slice) for x in key[1])
+                )
+                and key[1] in self.obj.columns
+            ):
+                obj = self.obj[key[1]]
+                if isinstance(obj, ABCSeries) and isinstance(
+                    value, (ABCSeries, Index, ExtensionArray, np.ndarray)
+                ):
+                    # check necessary in case of non-unique columns
+                    if obj.dtype != value.dtype:
+                        warnings.warn(
+                            "Setting `df.loc[:, col] = values` does *not* change "
+                            "the dtype of `df[col]`. It writes the entries from "
+                            "`values` into the existing array behind `df[col]`. "
+                            "To swap out the old array for the new one, use "
+                            "`df[col] = values` instead.",
+                            UserWarning,
+                            stacklevel=find_stack_level(),
+                        )
+        # TODO: the checks above handle the most common cases, but miss
+        # a) obj.columns is MultiIndex
+        # b) non-unique columns
+        # c) df.loc[:, [col]] = ...
+
     def _validate_key(self, key, axis: AxisInt) -> None:
         """
         Ensure that key is valid for current indexer.
diff --git a/pandas/tests/copy_view/test_indexing.py b/pandas/tests/copy_view/test_indexing.py
index 37a21e1098e78..7d4b4f6562e23 100644
--- a/pandas/tests/copy_view/test_indexing.py
+++ b/pandas/tests/copy_view/test_indexing.py
@@ -308,7 +308,10 @@ def test_subset_set_column_with_loc(backend, dtype):
     df_orig = df.copy()
     subset = df[1:3]
 
-    subset.loc[:, "a"] = np.array([10, 11], dtype="int64")
+    msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+    err = UserWarning if backend[0] != "numpy" else None
+    with tm.assert_produces_warning(err, match=msg):
+        subset.loc[:, "a"] = np.array([10, 11], dtype="int64")
 
     subset._mgr._verify_integrity()
     expected = DataFrame(
diff --git a/pandas/tests/frame/indexing/test_setitem.py b/pandas/tests/frame/indexing/test_setitem.py
index c0fead4889932..37e927bf3c3ba 100644
--- a/pandas/tests/frame/indexing/test_setitem.py
+++ b/pandas/tests/frame/indexing/test_setitem.py
@@ -792,7 +792,9 @@ def test_setitem_frame_midx_columns(self):
     def test_loc_setitem_ea_dtype(self):
         # GH#55604
         df = DataFrame({"a": np.array([10], dtype="i8")})
-        df.loc[:, "a"] = Series([11], dtype="Int64")
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+        with tm.assert_produces_warning(UserWarning, match=msg):
+            df.loc[:, "a"] = Series([11], dtype="Int64")
         expected = DataFrame({"a": np.array([11], dtype="i8")})
         tm.assert_frame_equal(df, expected)
 
diff --git a/pandas/tests/indexing/test_iloc.py b/pandas/tests/indexing/test_iloc.py
index ddb58ecbfa6f3..623a47383ff30 100644
--- a/pandas/tests/indexing/test_iloc.py
+++ b/pandas/tests/indexing/test_iloc.py
@@ -87,7 +87,12 @@ def test_iloc_setitem_fullcol_categorical(self, indexer_li, key):
         df = frame.copy()
         orig_vals = df.values
 
-        indexer_li(df)[key, 0] = cat
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+        err = None
+        if isinstance(key, slice) and key == slice(None):
+            err = UserWarning
+        with tm.assert_produces_warning(err, match=msg):
+            indexer_li(df)[key, 0] = cat
 
         expected = DataFrame({0: cat}).astype(object)
         assert np.shares_memory(df[0].values, orig_vals)
@@ -103,7 +108,8 @@ def test_iloc_setitem_fullcol_categorical(self, indexer_li, key):
         #  we retain the object dtype.
         frame = DataFrame({0: np.array([0, 1, 2], dtype=object), 1: range(3)})
         df = frame.copy()
-        indexer_li(df)[key, 0] = cat
+        with tm.assert_produces_warning(err, match=msg):
+            indexer_li(df)[key, 0] = cat
         expected = DataFrame({0: Series(cat.astype(object), dtype=object), 1: range(3)})
         tm.assert_frame_equal(df, expected)
 
@@ -1521,10 +1527,12 @@ def test_iloc_setitem_pure_position_based(self):
     def test_iloc_nullable_int64_size_1_nan(self):
         # GH 31861
         result = DataFrame({"a": ["test"], "b": [np.nan]})
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
 
         ser = Series([NA], name="b", dtype="Int64")
         with pytest.raises(TypeError, match="Invalid value"):
-            result.loc[:, "b"] = ser
+            with tm.assert_produces_warning(UserWarning, match=msg):
+                result.loc[:, "b"] = ser
 
     def test_iloc_arrow_extension_array(self):
         # GH#61311
diff --git a/pandas/tests/indexing/test_indexing.py b/pandas/tests/indexing/test_indexing.py
index 113eb6c2b2c31..1a611dcf54f20 100644
--- a/pandas/tests/indexing/test_indexing.py
+++ b/pandas/tests/indexing/test_indexing.py
@@ -548,7 +548,9 @@ def test_astype_assignment(self, using_infer_string):
 
         # GH5702 (loc)
         df = df_orig.copy()
-        df.loc[:, "A"] = df.loc[:, "A"].astype(np.int64)
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+        with tm.assert_produces_warning(UserWarning, match=msg):
+            df.loc[:, "A"] = df.loc[:, "A"].astype(np.int64)
         expected = DataFrame(
             [[1, "2", "3", ".4", 5, 6.0, "foo"]], columns=list("ABCDEFG")
         )
@@ -570,12 +572,14 @@ def test_astype_assignment_full_replacements(self):
 
         # With the enforcement of GH#45333 in 2.0, this assignment occurs inplace,
         #  so float64 is retained
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
         df.iloc[:, 0] = df["A"].astype(np.int64)
         expected = DataFrame({"A": [1.0, 2.0, 3.0, 4.0]})
         tm.assert_frame_equal(df, expected)
 
         df = DataFrame({"A": [1.0, 2.0, 3.0, 4.0]})
-        df.loc[:, "A"] = df["A"].astype(np.int64)
+        with tm.assert_produces_warning(UserWarning, match=msg):
+            df.loc[:, "A"] = df["A"].astype(np.int64)
         tm.assert_frame_equal(df, expected)
 
     @pytest.mark.parametrize("indexer", [tm.getitem, tm.loc])
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index de2d914aab229..37f5fea1d749c 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -581,8 +581,11 @@ def test_loc_setitem_consistency(self, frame_for_consistency, val):
         # GH 6149
         # coerce similarly for setitem and loc when rows have a null-slice
         df = frame_for_consistency.copy()
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+        err = UserWarning if isinstance(val, np.ndarray) else None
         with pytest.raises(TypeError, match="Invalid value"):
-            df.loc[:, "date"] = val
+            with tm.assert_produces_warning(err, match=msg):
+                df.loc[:, "date"] = val
 
     def test_loc_setitem_consistency_dt64_to_str(self, frame_for_consistency):
         # GH 6149
@@ -646,18 +649,21 @@ def test_loc_setitem_consistency_slice_column_len(self, using_infer_string):
         ]
         df = DataFrame(values, index=mi, columns=cols)
 
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
         ctx = contextlib.nullcontext()
         if using_infer_string:
             ctx = pytest.raises(TypeError, match="Invalid value")
 
         with ctx:
-            df.loc[:, ("Respondent", "StartDate")] = to_datetime(
-                df.loc[:, ("Respondent", "StartDate")]
-            )
+            with tm.assert_produces_warning(UserWarning, match=msg):
+                df.loc[:, ("Respondent", "StartDate")] = to_datetime(
+                    df.loc[:, ("Respondent", "StartDate")]
+                )
         with ctx:
-            df.loc[:, ("Respondent", "EndDate")] = to_datetime(
-                df.loc[:, ("Respondent", "EndDate")]
-            )
+            with tm.assert_produces_warning(UserWarning, match=msg):
+                df.loc[:, ("Respondent", "EndDate")] = to_datetime(
+                    df.loc[:, ("Respondent", "EndDate")]
+                )
 
         if using_infer_string:
             # infer-objects won't infer stuff anymore
@@ -1426,7 +1432,9 @@ def test_loc_setitem_single_row_categorical(self, using_infer_string):
 
         # pre-2.0 this swapped in a new array, in 2.0 it operates inplace,
         #  consistent with non-split-path
-        df.loc[:, "Alpha"] = categories
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+        with tm.assert_produces_warning(UserWarning, match=msg):
+            df.loc[:, "Alpha"] = categories
 
         result = df["Alpha"]
         expected = Series(categories, index=df.index, name="Alpha").astype(
diff --git a/pandas/tests/indexing/test_partial.py b/pandas/tests/indexing/test_partial.py
index 6f20d0e4e7cbf..11fa4d4b5ac80 100644
--- a/pandas/tests/indexing/test_partial.py
+++ b/pandas/tests/indexing/test_partial.py
@@ -318,7 +318,9 @@ def test_partial_setting_frame(self):
         df["B"] = df["B"].astype(np.float64)
         # as of 2.0, df.loc[:, "B"] = ... attempts (and here succeeds) at
         #  setting inplace
-        df.loc[:, "B"] = df.loc[:, "A"]
+        msg = r"Setting `df.loc\[:, col\] = values` does \*not\* change"
+        with tm.assert_produces_warning(UserWarning, match=msg):
+            df.loc[:, "B"] = df.loc[:, "A"]
         tm.assert_frame_equal(df, expected)
 
         # single dtype frame, partial setting