diff --git a/CHANGELOG.md b/CHANGELOG.md
index 8883ce517da74..365ad2fce3e83 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -6,6 +6,14 @@
 
 - No longer provide mypyc-accelerated wheels for macOS x86_64 [mypyc-wheels #119](https://github.com/mypyc/mypy_mypyc-wheels/pull/119)
 
+### Documentation Updates
+
+- Clarify that nested `Any` in an overload argument is ambiguous, the same as a top-level `Any` (PR [21897](https://github.com/python/mypy/pull/21897))
+
+### Other Notable Fixes and Improvements
+
+- Treat type aliases that expand to `Any` (or a type containing `Any`) as ambiguous in overload matching, matching a written `Any` (PR [21897](https://github.com/python/mypy/pull/21897))
+
 ## Mypy 2.3
 
 We've just uploaded mypy 2.3.0 to the Python Package Index ([PyPI](https://pypi.org/project/mypy/)).
diff --git a/docs/source/more_types.rst b/docs/source/more_types.rst
index 444753757aad9..3a24e4a5f2d63 100644
--- a/docs/source/more_types.rst
+++ b/docs/source/more_types.rst
@@ -394,8 +394,10 @@ will have an inferred type of ``float``. The implementer is responsible
 for making sure ``summarize`` breaks ties in the same way at runtime.
 
 However, there are two exceptions to the "pick the first match" rule.
-First, if multiple variants match due to an argument being of type
-``Any``, mypy will make the inferred type also be ``Any``:
+First, if multiple variants match because an argument has type ``Any``
+or *contains* ``Any`` (for example ``list[Any]`` or ``Sequence[Any]``,
+including via a type alias), mypy will make the inferred type also be
+``Any``:
 
 .. code-block:: python
 
@@ -404,6 +406,18 @@ First, if multiple variants match due to an argument being of type
     # output2 is of type 'Any'
     output2 = summarize(dynamic_var)
 
+    nested_any: list[Any] = some_dynamic_function()
+
+    # output2_nested is also 'Any'. A list[Any] is not "really" a list[int]:
+    # it can hold strings, and list[str] selects the other overload. The
+    # call is therefore ambiguous in the same way as a top-level Any.
+    output2_nested = summarize(nested_any)
+
+    Nested = list[Any]
+    aliased: Nested = some_dynamic_function()
+    # output2_alias is also 'Any': a type alias does not hide the nested Any.
+    output2_alias = summarize(aliased)
+
 Second, if multiple variants match due to one or more of the arguments
 being a union, mypy will make the inferred type be the union of the
 matching variant returns:
diff --git a/mypy/checkexpr.py b/mypy/checkexpr.py
index 172d44555b946..0c64ab270d65b 100644
--- a/mypy/checkexpr.py
+++ b/mypy/checkexpr.py
@@ -6638,9 +6638,23 @@ class HasAnyType(types.BoolTypeQuery):
     def __init__(self, ignore_in_type_obj: bool) -> None:
         super().__init__(types.ANY_STRATEGY)
         self.ignore_in_type_obj = ignore_in_type_obj
+        # Alias targets store a written `Any` as TypeOfAny.special_form.
+        # Count those as real Any while expanding aliases, so Nested = Sequence[Any]
+        # matches a direct Sequence[Any] for overload ambiguity.
+        self.count_alias_special_form_any = False
 
     def visit_any(self, t: AnyType) -> bool:
-        return t.type_of_any != TypeOfAny.special_form  # special forms are not real Any types
+        if t.type_of_any == TypeOfAny.special_form:
+            return self.count_alias_special_form_any
+        return True
+
+    def visit_type_alias_type(self, t: TypeAliasType) -> bool:
+        old = self.count_alias_special_form_any
+        self.count_alias_special_form_any = True
+        try:
+            return super().visit_type_alias_type(t)
+        finally:
+            self.count_alias_special_form_any = old
 
     def visit_callable_type(self, t: CallableType) -> bool:
         if self.ignore_in_type_obj and t.is_type_obj():
@@ -6855,6 +6869,13 @@ def any_causes_overload_ambiguity(
 ) -> bool:
     """May an argument containing 'Any' cause ambiguous result type on call to overloaded function?
 
+    This includes nested Any, such as Sequence[Any] or list[Any], not just a
+    top-level Any, and the same types reached through a type alias. A nested
+    Any can materialize as different concrete types, so if several overloads
+    remain and their return types differ, the result is Any.
+    (If every materialization matched an earlier overload, the spec would drop
+    later ones; this helper over-approximates that case as ambiguous.)
+
     Note that this sometimes returns True even if there is no ambiguity, since a correct
     implementation would be complex (and the call would be imprecisely typed due to Any
     types anyway).
diff --git a/test-data/unit/check-overloading.test b/test-data/unit/check-overloading.test
index 721ca52f59eed..2067d98938ddb 100644
--- a/test-data/unit/check-overloading.test
+++ b/test-data/unit/check-overloading.test
@@ -1906,6 +1906,240 @@ a: Any
 reveal_type(f(a))     # N: Revealed type is "def (*Any, **Any) -> Any"
 reveal_type(f(a)(a))  # N: Revealed type is "Any"
 
+[case testOverloadNestedAnyInGenericArgumentIsAmbiguous]
+# https://github.com/python/mypy/issues/21768
+# Nested Any is treated like top-level Any for overload matching.
+# Sequence[Any] can materialize as Sequence[int] (first overload) or as
+# another sequence type (only the object overload), so the result is Any.
+from typing import Any, Mapping, Sequence, overload
+
+@overload
+def f(s: Sequence[int]) -> int: ...
+@overload
+def f(s: object) -> object: ...
+def f(s): pass
+
+concrete: Sequence[int]
+nested_any: Sequence[Any]
+top_level_any: Any
+reveal_type(f(concrete))  # N: Revealed type is "builtins.int"
+reveal_type(f(nested_any))  # N: Revealed type is "Any"
+reveal_type(f(top_level_any))  # N: Revealed type is "Any"
+
+@overload
+def g(s: Mapping[str, int]) -> int: ...
+@overload
+def g(s: object) -> object: ...
+def g(s): pass
+
+mapping_any: Mapping[str, Any]
+reveal_type(g(mapping_any))  # N: Revealed type is "Any"
+
+[case testOverloadNestedAnyUnambiguousWhenReturnsMatch]
+# If remaining overloads agree on the return type, nested Any is not ambiguous.
+from typing import Any, Sequence, overload
+
+@overload
+def f(s: Sequence[int]) -> str: ...
+@overload
+def f(s: object) -> str: ...
+def f(s): pass
+
+nested_any: Sequence[Any]
+reveal_type(f(nested_any))  # N: Revealed type is "builtins.str"
+
+[case testOverloadNestedAnyDoesNotForceAnyWhenOtherArgSelects]
+# Nested Any does not collapse the result when it does not itself cause
+# multiple overloads with differing returns to remain.
+from typing import Any, Sequence, overload
+
+@overload
+def f(x: Sequence[int], y: int) -> int: ...
+@overload
+def f(x: Sequence[int], y: str) -> str: ...
+def f(x, y): pass
+
+nested_any: Sequence[Any]
+reveal_type(f(nested_any, 1))  # N: Revealed type is "builtins.int"
+reveal_type(f(nested_any, "x"))  # N: Revealed type is "builtins.str"
+a: Any
+reveal_type(f(nested_any, a))  # N: Revealed type is "Any"
+
+[case testOverloadNestedAnyWithIncompatibleOverlappingReturns]
+# Issue 21768's original pair also has unsafely overlapping returns.
+# The overlap error is separate; the call-site result is still Any.
+from typing import Any, Sequence, overload
+
+@overload
+def f(s: Sequence[int]) -> str: ...  # E: Overloaded function signatures 1 and 2 overlap with incompatible return types
+@overload
+def f(s: object) -> int: ...
+def f(s): pass
+
+concrete: Sequence[int]
+nested_any: Sequence[Any]
+reveal_type(f(concrete))  # N: Revealed type is "builtins.str"
+reveal_type(f(nested_any))  # N: Revealed type is "Any"
+
+[case testOverloadNestedAnyInhabitationCounterexample]
+# Picking the Sequence[int] overload for Sequence[Any] is unsound:
+# a Sequence[str] inhabits Sequence[Any], and that call takes the object
+# overload (int), not str. See typing spec overload call evaluation step 5.
+from typing import Any, Sequence, overload
+
+@overload
+def f(s: Sequence[int]) -> str: ...  # E: Overloaded function signatures 1 and 2 overlap with incompatible return types
+@overload
+def f(s: object) -> int: ...
+def f(s): pass
+
+as_str: Sequence[str]
+nested_any: Sequence[Any] = as_str
+reveal_type(f(as_str))  # N: Revealed type is "builtins.int"
+reveal_type(f(nested_any))  # N: Revealed type is "Any"
+
+[case testOverloadNestedAnyOnlyOneOverloadMatches]
+# Nested Any is not a blunt "always Any" switch. If only one overload
+# is compatible, that overload wins even when the argument contains Any.
+from typing import Any, Sequence, overload
+
+@overload
+def f(s: Sequence[int]) -> str: ...
+@overload
+def f(s: str) -> int: ...
+def f(s): pass
+
+nested_any: Sequence[Any]
+reveal_type(f(nested_any))  # N: Revealed type is "builtins.str"
+reveal_type(f("x"))  # N: Revealed type is "builtins.int"
+
+[case testOverloadNestedAnySpecExampleThreeOverloads]
+# Spec step-5 example: every materialization of list[Any] matches the
+# first or second overload, so the Any fallback is dropped. The first
+# two remain with different returns, so the call is still Any.
+# Picking the first overload here would be the #21768 "fix" and is wrong.
+from typing import Any, overload
+
+@overload
+def example(x: list[int]) -> int: ...
+@overload
+def example(x: list[Any]) -> str: ...
+@overload
+def example(x: Any) -> bytes: ...
+def example(x): pass
+
+a: list[Any]
+reveal_type(example(a))  # N: Revealed type is "Any"
+
+[case testOverloadNestedAnyMatchesExistingListMatrix]
+# Already locked in by testOverloadsUsingAny: invariant list[int]/list[str]
+# with a list[Any] argument is Any. Repeated here next to the #21768 cases
+# so that matrix cannot drift from the Sequence[Any] rule.
+from typing import Any, List, overload
+
+@overload
+def foo(x: List[int]) -> int: ...
+@overload
+def foo(x: List[str]) -> str: ...
+def foo(x): pass
+
+c: List[Any]
+reveal_type(foo(c))  # N: Revealed type is "Any"
+[builtins fixtures/list.pyi]
+
+[case testOverloadNestedAnyInDictValues]
+from typing import Any, overload
+
+@overload
+def f(s: dict[str, int]) -> int: ...
+@overload
+def f(s: object) -> object: ...
+def f(s): pass
+
+d: dict[str, Any]
+reveal_type(f(d))  # N: Revealed type is "Any"
+[builtins fixtures/dict.pyi]
+
+[case testOverloadNestedAnyInFixedTuple]
+from typing import Any, overload
+
+@overload
+def g(s: tuple[int, int]) -> str: ...  # E: Overloaded function signatures 1 and 2 overlap with incompatible return types
+@overload
+def g(s: object) -> int: ...
+def g(s): pass
+
+t: tuple[Any, int]
+reveal_type(g(t))  # N: Revealed type is "Any"
+[builtins fixtures/tuple.pyi]
+
+[case testOverloadNestedAnyOnMethod]
+from typing import Any, Sequence, overload
+
+class Box:
+    @overload
+    def get(self, key: Sequence[int]) -> int: ...
+    @overload
+    def get(self, key: object) -> object: ...
+    def get(self, key): pass
+
+nested_any: Sequence[Any]
+reveal_type(Box().get(nested_any))  # N: Revealed type is "Any"
+
+[case testOverloadNestedAnyViaTypeAliasIsAmbiguous]
+# A type alias must not hide nested Any from overload matching. Alias targets
+# store written Any as a special form; that is still Any (#15630, #21768).
+from typing import Any, Sequence, overload
+
+Nested = Sequence[Any]
+
+@overload
+def f(s: Sequence[int]) -> int: ...
+@overload
+def f(s: object) -> object: ...
+def f(s): pass
+
+direct: Sequence[Any]
+aliased: Nested
+reveal_type(f(direct))  # N: Revealed type is "Any"
+reveal_type(f(aliased))  # N: Revealed type is "Any"
+
+[case testOverloadBareAnyTypeAliasIsAmbiguous]
+# https://github.com/python/mypy/issues/15630
+from typing import Any, overload
+
+TypeSpec = Any
+
+@overload
+def f(x: int) -> int: ...
+@overload
+def f(x: object) -> object: ...
+def f(x): pass
+
+a: Any
+b: TypeSpec
+reveal_type(f(a))  # N: Revealed type is "Any"
+reveal_type(f(b))  # N: Revealed type is "Any"
+
+[case testOverloadBareAnyTypeAliasDoesNotPickFirstForIdentity]
+# The #15630 reproducer: an alias to Any must not pick the first overload.
+from typing import Any, Union, overload
+
+@overload
+def my_origin(x: type) -> type: ...
+@overload
+def my_origin(x: Any) -> Any: ...
+def my_origin(x):
+    return x
+
+TypeSpec = Any
+
+def call_any(spec: Any) -> bool:
+    return my_origin(spec) is Union
+
+def call_alias(spec: TypeSpec) -> bool:
+    return my_origin(spec) is Union
+
 [case testOverloadOnOverloadWithType]
 from typing import Any, Type, TypeVar, overload
 from mod import MyInt
diff --git a/test-data/unit/pythoneval.test b/test-data/unit/pythoneval.test
index 8c37e48d7c332..9dc6f311745b0 100644
--- a/test-data/unit/pythoneval.test
+++ b/test-data/unit/pythoneval.test
@@ -1346,6 +1346,42 @@ def print_custom_table() -> None:
 [out]
 _testLoadsOfOverloads.py:24: note: Revealed type is "str"
 
+[case testOverloadNestedAnyWithFullStubs]
+# Full-stub counterpart of #21768: collections.abc.Sequence, dict, tuple.
+from collections.abc import Sequence
+from typing import Any, overload
+
+@overload
+def f(s: Sequence[int]) -> int: ...
+@overload
+def f(s: object) -> object: ...
+def f(s: object) -> object:
+    return 0
+
+concrete: Sequence[int] = [1]
+nested: Sequence[Any] = [1]
+as_str: Sequence[str] = ["x"]
+print(f(concrete), f(nested), f(as_str))
+reveal_type(f(concrete))
+reveal_type(f(nested))
+reveal_type(f(as_str))
+
+@overload
+def g(s: dict[str, int]) -> int: ...
+@overload
+def g(s: object) -> object: ...
+def g(s: object) -> object:
+    return 0
+
+d: dict[str, Any] = {"a": 1}
+print(g(d))
+reveal_type(g(d))
+[out]
+_testOverloadNestedAnyWithFullStubs.py:16: note: Revealed type is "int"
+_testOverloadNestedAnyWithFullStubs.py:17: note: Revealed type is "Any"
+_testOverloadNestedAnyWithFullStubs.py:18: note: Revealed type is "object"
+_testOverloadNestedAnyWithFullStubs.py:29: note: Revealed type is "Any"
+
 [case testReduceWithAnyInstance]
 from typing import Iterable
 from functools import reduce