diff --git a/msgspec/_core.c b/msgspec/_core.c
index 507eda8a..8ca24066 100644
--- a/msgspec/_core.c
+++ b/msgspec/_core.c
@@ -7173,6 +7173,28 @@ Struct_richcompare(PyObject *self, PyObject *other, int op) {
         Py_RETURN_NOTIMPLEMENTED;
     }
 
+    if (
+        MS_UNLIKELY(op == Py_NE && (Py_TYPE(self)->tp_richcompare != Struct_richcompare))
+    ) {
+        /* This case is hit when a subclass has manually defined `__eq__` but
+         * not `__ne__`. In this case we want to dispatch to `__eq__` and invert
+         * the result, rather than relying on the default `__ne__` implementation.
+         */
+        PyObject *out = Py_TYPE(self)->tp_richcompare(self, other, Py_EQ);
+        if (out != NULL && out != Py_NotImplemented) {
+            int is_true = PyObject_IsTrue(out);
+            Py_DECREF(out);
+            if (is_true < 0) {
+                out = NULL;
+            }
+            else {
+                out = is_true ? Py_False : Py_True;
+                Py_INCREF(out);
+            }
+        }
+        return out;
+    }
+
     int equal = 1;
     PyObject *left = NULL, *right = NULL;
 
diff --git a/tests/test_struct.py b/tests/test_struct.py
index 80255f52..d00b7e4a 100644
--- a/tests/test_struct.py
+++ b/tests/test_struct.py
@@ -1562,6 +1562,21 @@ class Test2(Test):
         self.assert_neq(x, Test(2, 2))
         self.assert_neq(x, Test2(1, 2))
 
+    def test_struct_override_eq(self):
+        class Ex(Struct):
+            a: int
+            b: int
+
+            def __eq__(self, other):
+                return self.a == other.a
+
+        x = Ex(1, 2)
+        y = Ex(1, 3)
+        z = Ex(2, 3)
+
+        self.assert_eq(x, y)
+        self.assert_neq(x, z)
+
     def test_struct_eq_identity_fastpath(self):
         class Bad:
             def __eq__(self, other):