diff --git a/mypyc/irbuild/prepare.py b/mypyc/irbuild/prepare.py
index 15a82b1f719c6..906a4fe46a2f7 100644
--- a/mypyc/irbuild/prepare.py
+++ b/mypyc/irbuild/prepare.py
@@ -26,6 +26,7 @@
     Decorator,
     Expression,
     FuncDef,
+    IndexExpr,
     MemberExpr,
     MypyFile,
     NameExpr,
@@ -118,6 +119,12 @@ def build_type_map(
                     module.path, module.fullname, cdef, errors, mapper, options
                 )
 
+    # Validate cross-class properties after all ClassIR flags are populated.
+    for module, cdef in classes:
+        with catch_errors(module.path, cdef.line):
+            if mapper.type_to_ir[cdef.info].is_ext_class:
+                validate_acyclic_class_bases(module.path, cdef, errors, mapper)
+
     # Prepare implicit attribute accessors as needed if an attribute overrides a property.
     for module, cdef in classes:
         class_ir = mapper.type_to_ir[cdef.info]
@@ -345,6 +352,51 @@ def can_subclass_builtin(builtin_base: str) -> bool:
     )
 
 
+def get_removed_base_fullname(expr: Expression) -> str | None:
+    if isinstance(expr, IndexExpr):
+        expr = expr.base
+    if isinstance(expr, RefExpr):
+        return expr.fullname
+    return None
+
+
+def find_non_acyclic_base(cdef: ClassDef, mapper: Mapper) -> str | None:
+    if cdef.type_args:
+        return "typing.Generic"
+
+    for expr in cdef.removed_base_type_exprs:
+        if fullname := get_removed_base_fullname(expr):
+            return fullname
+        return "a removed base class"
+
+    for base in cdef.info.mro[1:]:
+        if base.fullname == "builtins.object":
+            continue
+
+        base_ir = mapper.type_to_ir.get(base)
+        if base_ir is not None and base_ir.is_acyclic:
+            continue
+
+        return base.fullname
+
+    return None
+
+
+def validate_acyclic_class_bases(
+    path: str, cdef: ClassDef, errors: Errors, mapper: Mapper
+) -> None:
+    ir = mapper.type_to_ir[cdef.info]
+    if not ir.is_acyclic:
+        return
+
+    if fullname := find_non_acyclic_base(cdef, mapper):
+        errors.error(
+            f'"acyclic" can\'t be used in a class that inherits from non-acyclic type "{fullname}"',
+            path,
+            cdef.line,
+        )
+
+
 def prepare_class_def(
     path: str,
     module_name: str,
diff --git a/mypyc/test-data/irbuild-classes.test b/mypyc/test-data/irbuild-classes.test
index 22b8d888c168a..2f5ecfd751040 100644
--- a/mypyc/test-data/irbuild-classes.test
+++ b/mypyc/test-data/irbuild-classes.test
@@ -2138,6 +2138,47 @@ class NonNative:
 class InterpSub:
     pass
 
+[case testAcyclicClassRequiresAcyclicBases]
+from typing import Generic, TypeVar
+from mypy_extensions import mypyc_attr, trait
+
+T = TypeVar("T")
+
+class NonAcyclicBase:
+    pass
+
+@trait
+class TraitBase:
+    pass
+
+@mypyc_attr(native_class=False)
+class NonNativeBase:
+    pass
+
+@mypyc_attr(acyclic=True)
+class AcyclicBase:
+    pass
+
+@mypyc_attr(acyclic=True)
+class GoodDerived(AcyclicBase):
+    pass
+
+@mypyc_attr(acyclic=True)
+class BadDerived(NonAcyclicBase):  # E: "acyclic" can't be used in a class that inherits from non-acyclic type "__main__.NonAcyclicBase"
+    pass
+
+@mypyc_attr(acyclic=True)
+class BadGeneric(Generic[T]):  # E: "acyclic" can't be used in a class that inherits from non-acyclic type "typing.Generic"
+    pass
+
+@mypyc_attr(acyclic=True)
+class BadDerivedTrait(TraitBase):  # E: "acyclic" can't be used in a class that inherits from non-acyclic type "__main__.TraitBase"
+    pass
+
+@mypyc_attr(acyclic=True)
+class BadDerivedNonNative(NonNativeBase):  # E: "acyclic" can't be used in a class that inherits from non-acyclic type "__main__.NonNativeBase"
+    pass
+
 [case testUnsupportedGetAttr]
 from mypy_extensions import mypyc_attr
 
diff --git a/mypyc/test-data/irbuild-python312.test b/mypyc/test-data/irbuild-python312.test
new file mode 100644
index 0000000000000..12f3bfae687c6
--- /dev/null
+++ b/mypyc/test-data/irbuild-python312.test
@@ -0,0 +1,6 @@
+[case testAcyclicGenericIsRejected_python3_12]
+from mypy_extensions import mypyc_attr
+
+@mypyc_attr(acyclic=True)
+class BadGeneric[T]:  # E: "acyclic" can't be used in a class that inherits from non-acyclic type "typing.Generic"
+    pass
diff --git a/mypyc/test/test_irbuild.py b/mypyc/test/test_irbuild.py
index 6fa7d3979d2ed..f1f0ec777c3da 100644
--- a/mypyc/test/test_irbuild.py
+++ b/mypyc/test/test_irbuild.py
@@ -64,6 +64,9 @@
     "irbuild-match.test",
 ]
 
+if sys.version_info >= (3, 12):
+    files.append("irbuild-python312.test")
+
 if sys.version_info >= (3, 14):
     files.append("irbuild-python314.test")