Self-grooming is a complex behavior with important biological functions and pathological relevance. How the brain coordinates with the spinal cord to generate the repetitive movements of self-grooming remains largely unknown. Here, we report that in the caudal part of the spinal trigeminal nucleus (Sp5C), neurons that express Cerebellin-2 (Cbln2+) form a neural circuit to the cervical spinal cord to maintain repetitive orofacial self-grooming. Inactivation of Cbln2+ Sp5C neurons blocked both sensory-evoked and stress-induced repetitive orofacial self-grooming. Activation of these neurons triggered short-latency repetitive forelimb movements that resembled orofacial self-grooming. The Cbln2+ Sp5C neurons were monosynaptically innervated by both somatosensory neurons in the trigeminal ganglion and paraventricular hypothalamic neurons. Among the divergent projections of Cbln2+ Sp5C neurons, a descending pathway that innervated motor neurons and interneurons in the cervical spinal cord was necessary and sufficient for repetitive orofacial self-grooming. These data reveal a brain-to-spinal sensorimotor loop for repetitive self-grooming in mice.