diff --git a/doc/source/whatsnew/v1.1.1.rst b/doc/source/whatsnew/v1.1.1.rst
index 3f177b29d52b8..85e2a335c55c6 100644
--- a/doc/source/whatsnew/v1.1.1.rst
+++ b/doc/source/whatsnew/v1.1.1.rst
@@ -16,10 +16,11 @@ Fixed regressions
 ~~~~~~~~~~~~~~~~~
 
 - Fixed regression where :meth:`DataFrame.to_numpy` would raise a ``RuntimeError`` for mixed dtypes when converting to ``str`` (:issue:`35455`)
-- Fixed regression where :func:`read_csv` would raise a ``ValueError`` when ``pandas.options.mode.use_inf_as_na`` was set to ``True`` (:issue:`35493`).
+- Fixed regression where :func:`read_csv` would raise a ``ValueError`` when ``pandas.options.mode.use_inf_as_na`` was set to ``True`` (:issue:`35493`)
 - Fixed regression where :func:`pandas.testing.assert_series_equal` would raise an error when non-numeric dtypes were passed with ``check_exact=True`` (:issue:`35446`)
 - Fixed regression in :class:`pandas.core.groupby.RollingGroupby` where column selection was ignored (:issue:`35486`)
 - Fixed regression in :meth:`DataFrame.shift` with ``axis=1`` and heterogeneous dtypes (:issue:`35488`)
+- Fixed regression in :meth:`DataFrame.diff` with read-only data (:issue:`35559`)
 - Fixed regression in ``.groupby(..).rolling(..)`` where a segfault would occur with ``center=True`` and an odd number of values (:issue:`35552`)
 - Fixed regression in :meth:`DataFrame.apply` where functions that altered the input in-place only operated on a single row (:issue:`35462`)
 - Fixed regression in :meth:`DataFrame.reset_index` would raise a ``ValueError`` on empty :class:`DataFrame` with a :class:`MultiIndex` with a ``datetime64`` dtype level (:issue:`35606`, :issue:`35657`)
diff --git a/pandas/_libs/algos.pyx b/pandas/_libs/algos.pyx
index 7e90a8cc681ef..0a70afda893cf 100644
--- a/pandas/_libs/algos.pyx
+++ b/pandas/_libs/algos.pyx
@@ -1200,14 +1200,15 @@ ctypedef fused out_t:
 @cython.boundscheck(False)
 @cython.wraparound(False)
 def diff_2d(
-    diff_t[:, :] arr,
-    out_t[:, :] out,
+    ndarray[diff_t, ndim=2] arr,  # TODO(cython 3) update to "const diff_t[:, :] arr"
+    ndarray[out_t, ndim=2] out,
     Py_ssize_t periods,
     int axis,
 ):
     cdef:
         Py_ssize_t i, j, sx, sy, start, stop
-        bint f_contig = arr.is_f_contig()
+        bint f_contig = arr.flags.f_contiguous
+        # bint f_contig = arr.is_f_contig()  # TODO(cython 3)
 
     # Disable for unsupported dtype combinations,
     #  see https://github.com/cython/cython/issues/2646
diff --git a/pandas/tests/frame/methods/test_diff.py b/pandas/tests/frame/methods/test_diff.py
index 45f134a93a23a..0486fb2d588b6 100644
--- a/pandas/tests/frame/methods/test_diff.py
+++ b/pandas/tests/frame/methods/test_diff.py
@@ -214,3 +214,12 @@ def test_diff_integer_na(self, axis, expected):
         # Test case for default behaviour of diff
         result = df.diff(axis=axis)
         tm.assert_frame_equal(result, expected)
+
+    def test_diff_readonly(self):
+        # https://github.com/pandas-dev/pandas/issues/35559
+        arr = np.random.randn(5, 2)
+        arr.flags.writeable = False
+        df = pd.DataFrame(arr)
+        result = df.diff()
+        expected = pd.DataFrame(np.array(df)).diff()
+        tm.assert_frame_equal(result, expected)
diff --git a/setup.py b/setup.py
index 43d19d525876b..f6f0cd9aabc0e 100755
--- a/setup.py
+++ b/setup.py
@@ -456,6 +456,9 @@ def run(self):
     if sys.version_info[:2] == (3, 8):  # GH 33239
         extra_compile_args.append("-Wno-error=deprecated-declarations")
 
+    # https://github.com/pandas-dev/pandas/issues/35559
+    extra_compile_args.append("-Wno-error=unreachable-code")
+
 # enable coverage by building cython files by setting the environment variable
 # "PANDAS_CYTHON_COVERAGE" (with a Truthy value) or by running build_ext
 # with `--with-cython-coverage`enabled