diff --git a/Lib/test/test_typing.py b/Lib/test/test_typing.py
index 459af253e2ce14..c84ff0f0a24ac0 100644
--- a/Lib/test/test_typing.py
+++ b/Lib/test/test_typing.py
@@ -1604,6 +1604,16 @@ class P(Protocol):
         with self.assertRaisesRegex(TypeError, "@runtime_checkable"):
             isinstance(1, P)
 
+    def test_super_call_init(self):
+        class P(Protocol):
+            x: int
+
+        class Foo(P):
+            def __init__(self):
+                super().__init__()
+
+        Foo()  # Previously triggered RecursionError
+
 
 class GenericTests(BaseTestCase):
 
diff --git a/Lib/typing.py b/Lib/typing.py
index 24f834e19aad28..5873d536a9ec44 100644
--- a/Lib/typing.py
+++ b/Lib/typing.py
@@ -1404,6 +1404,11 @@ def _no_init_or_replace_init(self, *args, **kwargs):
     if cls._is_protocol:
         raise TypeError('Protocols cannot be instantiated')
 
+    # Already using a custom `__init__`. No need to calculate correct
+    # `__init__` to call. This can lead to RecursionError. See bpo-45121.
+    if cls.__init__ is not _no_init_or_replace_init:
+        return
+
     # Initially, `__init__` of a protocol subclass is set to `_no_init_or_replace_init`.
     # The first instantiation of the subclass will call `_no_init_or_replace_init` which
     # searches for a proper new `__init__` in the MRO. The new `__init__`
diff --git a/Misc/NEWS.d/next/Core and Builtins/2021-09-07-17-10-16.bpo-45121.iG-Hsf.rst b/Misc/NEWS.d/next/Core and Builtins/2021-09-07-17-10-16.bpo-45121.iG-Hsf.rst
new file mode 100644
index 00000000000000..19eb3314125167
--- /dev/null
+++ b/Misc/NEWS.d/next/Core and Builtins/2021-09-07-17-10-16.bpo-45121.iG-Hsf.rst	
@@ -0,0 +1,2 @@
+Fix issue where ``Protocol.__init__`` raises ``RecursionError`` when it's
+called directly or via ``super()``. Patch provided by Yurii Karabas.