diff --git a/mypy/semanal.py b/mypy/semanal.py
index fb6f299a37956..da58c95869667 100644
--- a/mypy/semanal.py
+++ b/mypy/semanal.py
@@ -2403,6 +2403,9 @@ def analyze_unbound_tvar(self, t: Type) -> tuple[str, TypeVarLikeExpr] | None:
         if isinstance(t, UnboundType):
             sym = self.lookup_qualified(t.name, t)
             if sym and sym.fullname in UNPACK_TYPE_NAMES:
+                if not t.args:
+                    # Unpack used without arguments, e.g. `Protocol[Unpack]`
+                    return None
                 inner_t = t.args[0]
                 if isinstance(inner_t, UnboundType):
                     return self.analyze_unbound_tvar_impl(inner_t, is_unpacked=True)
diff --git a/test-data/unit/check-typevar-tuple.test b/test-data/unit/check-typevar-tuple.test
index 7ca21b280aad0..ff5cdc8719bc6 100644
--- a/test-data/unit/check-typevar-tuple.test
+++ b/test-data/unit/check-typevar-tuple.test
@@ -2765,3 +2765,11 @@ def func(d: Callable[[Unpack[Ts]], T]) -> T: ...
 y = func[1, int] # E: Type application is only supported for generic classes \
                  # E: Invalid type: try using Literal[1] instead?
 [builtins fixtures/tuple.pyi]
+
+[case testTypeVarTupleUnpackWithoutArgsInProtocol]
+# https://github.com/python/mypy/issues/21467
+from typing import Protocol, Unpack
+
+class C(Protocol[Unpack]):  # E: Free type variable expected in Protocol[...]
+    pass
+[builtins fixtures/tuple.pyi]