diff --git a/mypyc/primitives/registry.py b/mypyc/primitives/registry.py
index 5e7ecb70f55d..07546663d08e 100644
--- a/mypyc/primitives/registry.py
+++ b/mypyc/primitives/registry.py
@@ -371,4 +371,5 @@ def load_address_op(name: str, type: RType, src: str) -> LoadAddressDescription:
 import mypyc.primitives.list_ops
 import mypyc.primitives.misc_ops
 import mypyc.primitives.str_ops
-import mypyc.primitives.tuple_ops  # noqa: F401
+import mypyc.primitives.tuple_ops
+import mypyc.primitives.weakref_ops  # noqa: F401
diff --git a/mypyc/primitives/weakref_ops.py b/mypyc/primitives/weakref_ops.py
new file mode 100644
index 000000000000..024f9fedd17f
--- /dev/null
+++ b/mypyc/primitives/weakref_ops.py
@@ -0,0 +1,21 @@
+from mypyc.ir.ops import ERR_MAGIC
+from mypyc.ir.rtypes import object_rprimitive
+from mypyc.primitives.registry import ERR_NEG_INT, function_op
+
+# Weakref operations
+
+new_ref_op = function_op(
+    name="weakref.ReferenceType",
+    arg_types=[object_rprimitive, object_rprimitive],
+    return_type=object_rprimitive,
+    c_function_name="PyWeakref_NewRef",
+    error_kind=ERR_MAGIC,
+)
+
+deref_op = function_op(
+    name="weakref.ReferenceType.__call__",
+    arg_types=[object_rprimitive],
+    return_type=object_rprimitive,
+    c_function_name="PyWeakref_GetRef",
+    error_kind=ERR_NEG_INT,
+)
diff --git a/mypyc/test-data/irbuild-weakref.test b/mypyc/test-data/irbuild-weakref.test
new file mode 100644
index 000000000000..1b8c894821e5
--- /dev/null
+++ b/mypyc/test-data/irbuild-weakref.test
@@ -0,0 +1,27 @@
+[case testWeakrefRefCallback]
+import weakref
+from typing import Any, Callable
+def f(x: object, cb: Callable[[object], Any]) -> object:
+    return weakref.ref(x, cb)()
+
+[out]
+def f(x, cb):
+    x, cb, r0, r1 :: object
+L0:
+    r0 = PyWeakref_NewRef(x, cb)
+    r1 = PyWeakref_GetRef(r0)
+    return r1
+
+[case testFromWeakrefRefCallback]
+from typing import Any, Callable
+from weakref import ref
+def f(x: object, cb: Callable[[object], Any]) -> object:
+    return ref(x, cb)()
+
+[out]
+def f(x, cb):
+    x, cb, r0, r1 :: object
+L0:
+    r0 = PyWeakref_NewRef(x, cb)
+    r1 = PyWeakref_GetRef(r0)
+    return r1
diff --git a/mypyc/test-data/run-weakref.test b/mypyc/test-data/run-weakref.test
new file mode 100644
index 000000000000..de2d5dd5bad2
--- /dev/null
+++ b/mypyc/test-data/run-weakref.test
@@ -0,0 +1,19 @@
+# Test cases for weakrefs (compile and run)
+
+[case testWeakrefRef]
+import asyncio
+import pytest  # type: ignore [import-not-found]
+from weakref import ref
+from mypy_extensions import mypyc_attr
+
+@mypyc_attr(native_class=False)
+class Object:
+    """some random weakreffable object"""
+    pass
+
+def test_weakref_ref_with_callback():
+    obj = Object()
+    r = ref(obj, lambda x: x)
+    assert r() is obj
+    obj = None
+    assert r() is None, r()
diff --git a/mypyc/test/test_irbuild.py b/mypyc/test/test_irbuild.py
index 9c0ad06416a7..d8f974ef201b 100644
--- a/mypyc/test/test_irbuild.py
+++ b/mypyc/test/test_irbuild.py
@@ -53,6 +53,7 @@
     "irbuild-constant-fold.test",
     "irbuild-glue-methods.test",
     "irbuild-math.test",
+    "irbuild-weakref.test",
 ]
 
 if sys.version_info >= (3, 10):
diff --git a/mypyc/test/test_run.py b/mypyc/test/test_run.py
index e5b7e2421433..cd32daee4bdc 100644
--- a/mypyc/test/test_run.py
+++ b/mypyc/test/test_run.py
@@ -69,6 +69,7 @@
     "run-dunders-special.test",
     "run-singledispatch.test",
     "run-attrs.test",
+    "run-weakref.test",
     "run-python37.test",
     "run-python38.test",
 ]