diff --git a/mypy/applytype.py b/mypy/applytype.py
index 51a10c7084cf..b32b88fa3276 100644
--- a/mypy/applytype.py
+++ b/mypy/applytype.py
@@ -103,6 +103,12 @@ def apply_generic_arguments(
     # Apply arguments to argument types.
     arg_types = [expand_type(at, id_to_type) for at in callable.arg_types]
 
+    # Apply arguments to TypeGuard if any.
+    if callable.type_guard is not None:
+        type_guard = expand_type(callable.type_guard, id_to_type)
+    else:
+        type_guard = None
+
     # The callable may retain some type vars if only some were applied.
     remaining_tvars = [tv for tv in tvars if tv.id not in id_to_type]
 
@@ -110,4 +116,5 @@ def apply_generic_arguments(
         arg_types=arg_types,
         ret_type=expand_type(callable.ret_type, id_to_type),
         variables=remaining_tvars,
+        type_guard=type_guard,
     )
diff --git a/mypy/checkexpr.py b/mypy/checkexpr.py
index ed6fd73acfa5..9737c3585a76 100644
--- a/mypy/checkexpr.py
+++ b/mypy/checkexpr.py
@@ -344,11 +344,6 @@ def visit_call_expr_inner(self, e: CallExpr, allow_none_return: bool = False) ->
                                         ret_type=self.object_type(),
                                         fallback=self.named_type('builtins.function'))
         callee_type = get_proper_type(self.accept(e.callee, type_context, always_allow_any=True))
-        if (isinstance(e.callee, RefExpr)
-                and isinstance(callee_type, CallableType)
-                and callee_type.type_guard is not None):
-            # Cache it for find_isinstance_check()
-            e.callee.type_guard = callee_type.type_guard
         if (self.chk.options.disallow_untyped_calls and
                 self.chk.in_checked_function() and
                 isinstance(callee_type, CallableType)
@@ -886,10 +881,19 @@ def check_call_expr_with_callee_type(self,
         # Unions are special-cased to allow plugins to act on each item in the union.
         elif member is not None and isinstance(object_type, UnionType):
             return self.check_union_call_expr(e, object_type, member)
-        return self.check_call(callee_type, e.args, e.arg_kinds, e,
-                               e.arg_names, callable_node=e.callee,
-                               callable_name=callable_name,
-                               object_type=object_type)[0]
+        ret_type, callee_type = self.check_call(
+            callee_type, e.args, e.arg_kinds, e,
+            e.arg_names, callable_node=e.callee,
+            callable_name=callable_name,
+            object_type=object_type,
+        )
+        proper_callee = get_proper_type(callee_type)
+        if (isinstance(e.callee, RefExpr)
+                and isinstance(proper_callee, CallableType)
+                and proper_callee.type_guard is not None):
+            # Cache it for find_isinstance_check()
+            e.callee.type_guard = proper_callee.type_guard
+        return ret_type
 
     def check_union_call_expr(self, e: CallExpr, object_type: UnionType, member: str) -> Type:
         """"Type check calling a member expression where the base type is a union."""
diff --git a/test-data/unit/check-typeguard.test b/test-data/unit/check-typeguard.test
index ecefce091405..64fc7ea695cb 100644
--- a/test-data/unit/check-typeguard.test
+++ b/test-data/unit/check-typeguard.test
@@ -547,3 +547,53 @@ accepts_typeguard(with_typeguard_a)  # E: Argument 1 to "accepts_typeguard" has
 accepts_typeguard(with_typeguard_b)
 accepts_typeguard(with_typeguard_c)
 [builtins fixtures/tuple.pyi]
+
+[case testTypeGuardWithIdentityGeneric]
+from typing import TypeVar
+from typing_extensions import TypeGuard
+
+_T = TypeVar("_T")
+
+def identity(val: _T) -> TypeGuard[_T]:
+    pass
+
+def func1(name: _T):
+    reveal_type(name)  # N: Revealed type is "_T`-1"
+    if identity(name):
+        reveal_type(name)  # N: Revealed type is "_T`-1"
+
+def func2(name: str):
+    reveal_type(name)  # N: Revealed type is "builtins.str"
+    if identity(name):
+        reveal_type(name)  # N: Revealed type is "builtins.str"
+[builtins fixtures/tuple.pyi]
+
+[case testTypeGuardWithGenericInstance]
+from typing import TypeVar, List
+from typing_extensions import TypeGuard
+
+_T = TypeVar("_T")
+
+def is_list_of_str(val: _T) -> TypeGuard[List[_T]]:
+    pass
+
+def func(name: str):
+    reveal_type(name)  # N: Revealed type is "builtins.str"
+    if is_list_of_str(name):
+        reveal_type(name)  # N: Revealed type is "builtins.list[builtins.str]"
+[builtins fixtures/tuple.pyi]
+
+[case testTypeGuardWithTupleGeneric]
+from typing import TypeVar, Tuple
+from typing_extensions import TypeGuard
+
+_T = TypeVar("_T")
+
+def is_two_element_tuple(val: Tuple[_T, ...]) -> TypeGuard[Tuple[_T, _T]]:
+    pass
+
+def func(names: Tuple[str, ...]):
+    reveal_type(names)  # N: Revealed type is "builtins.tuple[builtins.str, ...]"
+    if is_two_element_tuple(names):
+        reveal_type(names)  # N: Revealed type is "Tuple[builtins.str, builtins.str]"
+[builtins fixtures/tuple.pyi]