diff --git a/doc/source/whatsnew/v1.5.0.rst b/doc/source/whatsnew/v1.5.0.rst
index 0b450fab53137..0e5bde5fc29ae 100644
--- a/doc/source/whatsnew/v1.5.0.rst
+++ b/doc/source/whatsnew/v1.5.0.rst
@@ -910,6 +910,7 @@ Missing
 - Bug in :meth:`Series.fillna` and :meth:`DataFrame.fillna` with :class:`IntervalDtype` and incompatible value raising instead of casting to a common (usually object) dtype (:issue:`45796`)
 - Bug in :meth:`DataFrame.interpolate` with object-dtype column not returning a copy with ``inplace=False`` (:issue:`45791`)
 - Bug in :meth:`DataFrame.dropna` allows to set both ``how`` and ``thresh`` incompatible arguments (:issue:`46575`)
+- Bug in :meth:`DataFrame.replace` now works when ``pandas.NA`` is a value in the dara frame (:issue:`47480`)
 
 MultiIndex
 ^^^^^^^^^^
diff --git a/pandas/_libs/missing.pyx b/pandas/_libs/missing.pyx
index 9b470e95dc22b..906935bb12aae 100644
--- a/pandas/_libs/missing.pyx
+++ b/pandas/_libs/missing.pyx
@@ -409,7 +409,6 @@ class NAType(C_NAType):
     __rdivmod__ = _create_binary_propagating_op("__rdivmod__", is_divmod=True)
     # __lshift__ and __rshift__ are not implemented
 
-    __eq__ = _create_binary_propagating_op("__eq__")
     __ne__ = _create_binary_propagating_op("__ne__")
     __le__ = _create_binary_propagating_op("__le__")
     __lt__ = _create_binary_propagating_op("__lt__")
@@ -423,6 +422,12 @@ class NAType(C_NAType):
     __abs__ = _create_unary_propagating_op("__abs__")
     __invert__ = _create_unary_propagating_op("__invert__")
 
+    def __eq__(self, other):
+        if other is C_NA:
+            return True
+        else:
+            return False
+
     # pow has special
     def __pow__(self, other):
         if other is C_NA:
diff --git a/pandas/core/missing.py b/pandas/core/missing.py
index 57b0a95f803b1..391921deded1f 100644
--- a/pandas/core/missing.py
+++ b/pandas/core/missing.py
@@ -93,6 +93,7 @@ def mask_missing(arr: ArrayLike, values_to_mask) -> npt.NDArray[np.bool_]:
             pass
         else:
             new_mask = arr == x
+
             if not isinstance(new_mask, np.ndarray):
                 # usually BooleanArray
                 new_mask = new_mask.to_numpy(dtype=bool, na_value=False)
diff --git a/pandas/tests/frame/methods/test_replace.py b/pandas/tests/frame/methods/test_replace.py
index f7504e9173bf5..5e2d2d536e6ff 100644
--- a/pandas/tests/frame/methods/test_replace.py
+++ b/pandas/tests/frame/methods/test_replace.py
@@ -1567,3 +1567,10 @@ def test_replace_with_value_also_being_replaced(self):
         result = df.replace({0: 1, 1: np.nan})
         expected = DataFrame({"A": [1, np.nan, 2], "B": [np.nan, 1, 2]})
         tm.assert_frame_equal(result, expected)
+
+    def test_replace_with_pandas_NA(self):
+        # GH47480
+        df = DataFrame({"A": [pd.NA, 1, 2], "B": [1, 0, 2]})
+        result = df.replace(2, 3)
+        expected = DataFrame({"A": [pd.NA, 1, 3], "B": [1, 0, 3]})
+        tm.assert_frame_equal(result, expected)