diff --git a/doc/source/whatsnew/v2.2.0.rst b/doc/source/whatsnew/v2.2.0.rst
index d9ab0452c8334..fcd52c33be8d7 100644
--- a/doc/source/whatsnew/v2.2.0.rst
+++ b/doc/source/whatsnew/v2.2.0.rst
@@ -845,6 +845,7 @@ Indexing
 - Bug in :meth:`DataFrame.loc` mutating a boolean indexer when :class:`DataFrame` has a :class:`MultiIndex` (:issue:`56635`)
 - Bug in :meth:`DataFrame.loc` when setting :class:`Series` with extension dtype into NumPy dtype (:issue:`55604`)
 - Bug in :meth:`Index.difference` not returning a unique set of values when ``other`` is empty or ``other`` is considered non-comparable (:issue:`55113`)
+- Bug in :meth:`NDFrame.__setattr__` getting from a property before setting to it if extending :class:`DataFrame` with a property (:issue:`56773`)
 - Bug in setting :class:`Categorical` values into a :class:`DataFrame` with numpy dtypes raising ``RecursionError`` (:issue:`52927`)
 - Fixed bug when creating new column with missing values when setting a single string value (:issue:`56204`)
 
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index 73f9481e53dea..c080341f39c32 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -6291,44 +6291,38 @@ def __getattr__(self, name: str):
     @final
     def __setattr__(self, name: str, value) -> None:
         """
-        After regular attribute access, try setting the name
+        If it can be found nowhere else than the info_axis, it must be a column.
         This allows simpler access to columns for interactive use.
         """
-        # first try regular attribute access via __getattribute__, so that
-        # e.g. ``obj.x`` and ``obj.x = 4`` will always reference/modify
-        # the same attribute.
-
-        try:
-            object.__getattribute__(self, name)
-            return object.__setattr__(self, name, value)
-        except AttributeError:
-            pass
-
-        # if this fails, go on to more involved attribute setting
-        # (note that this matches __getattr__, above).
-        if name in self._internal_names_set:
-            object.__setattr__(self, name, value)
-        elif name in self._metadata:
-            object.__setattr__(self, name, value)
-        else:
+        if (
+            name not in self.__dict__
+            and name not in self._internal_names_set
+            and name not in self._metadata
+            and name in self._info_axis
+        ):
             try:
-                existing = getattr(self, name)
-                if isinstance(existing, Index):
-                    object.__setattr__(self, name, value)
-                elif name in self._info_axis:
-                    self[name] = value
-                else:
-                    object.__setattr__(self, name, value)
+                self[name] = value
             except (AttributeError, TypeError):
-                if isinstance(self, ABCDataFrame) and (is_list_like(value)):
-                    warnings.warn(
-                        "Pandas doesn't allow columns to be "
-                        "created via a new attribute name - see "
-                        "https://pandas.pydata.org/pandas-docs/"
-                        "stable/indexing.html#attribute-access",
-                        stacklevel=find_stack_level(),
-                    )
-                object.__setattr__(self, name, value)
+                pass
+            else:
+                return
+
+        if (
+            isinstance(self, ABCDataFrame)
+            and name not in self.__dict__
+            and not hasattr(type(self), name)
+            and name not in self._internal_names
+            and name not in self._metadata
+            and is_list_like(value)
+        ):
+            warnings.warn(
+                "Pandas doesn't allow columns to be "
+                "created via a new attribute name - see "
+                "https://pandas.pydata.org/pandas-docs/"
+                "stable/indexing.html#attribute-access",
+                stacklevel=find_stack_level(),
+            )
+        object.__setattr__(self, name, value)
 
     @final
     def _dir_additions(self) -> set[str]:
diff --git a/pandas/tests/generic/test_frame.py b/pandas/tests/generic/test_frame.py
index fc7aa9e7b2c46..1380b7fe3a53d 100644
--- a/pandas/tests/generic/test_frame.py
+++ b/pandas/tests/generic/test_frame.py
@@ -149,6 +149,70 @@ def test_set_attribute(self):
         assert df.y == 5
         tm.assert_series_equal(df["y"], Series([2, 4, 6], name="y"))
 
+    def test_setattr_doesnt_call_getattr(self):
+        # Test to assert setattr doesn't call getattr, resulting in potentially
+        # odd behavior for descriptors; this is a step towards pandas extensibility
+
+        from functools import cached_property
+
+        class FancyDescriptor:
+            def __get__(self, instance, owner):
+                if instance is None:
+                    return self
+                return instance.__dict__[self.__name__]
+
+            def __set__(self, instance, value):
+                instance.__dict__[self.__name__] = value
+
+            def __delete__(self, instance):
+                del instance.__dict__[self.__name__]
+
+            def __set_name__(self, owner, name):
+                self.__name__ = name
+
+        class Frame(DataFrame):
+            @cached_property
+            def scalar(self):
+                raise AttributeError
+
+            @cached_property
+            def vector(self):
+                raise AttributeError
+
+            @property
+            def scalar_(self):
+                return self.__dict__["scalar_"]
+
+            @scalar_.setter
+            def scalar_(self, value):
+                self.__dict__["scalar_"] = value
+
+            @property
+            def vector_(self):
+                return self.__dict__["vector_"]
+
+            @vector_.setter
+            def vector_(self, value):
+                self.__dict__["vector_"] = value
+
+            fancy = FancyDescriptor()
+
+        with tm.assert_produces_warning(False):
+            frame = Frame()
+            try:
+                frame.scalar = ...
+                frame.vector = [1, 2, 3]
+                frame.scalar_ = ...
+                frame.vector_ = [1, 2, 3]
+                frame.fancy = ...
+                del frame.fancy
+                frame.fancy = [1, 2, 3]
+            except (AttributeError, KeyError):
+                pytest.fail(
+                    "DataFrame.__setattr__ prematurely called "
+                    "getattr on the same name."
+                )
+
     def test_deepcopy_empty(self):
         # This test covers empty frame copying with non-empty column sets
         # as reported in issue GH15370