Focused ultrasound (US) can stimulate specific regions of the brain non-invasively in animals and humans. This new brain stimulation method has the potential to provide a spatially precise treatment of neurological disorders and to advance brain mapping. To realize this potential, it is crucial to discover how US stimulates neurons. Toward this end, we devised a genetic dissection assay leveraging the well-characterized nervous system of C. elegans nematodes. We found that focused US (0.6--1.0 MPa, 10 MHz) elicits robust reversal behavior in wild-type animals. The response is preserved in animals deficient in thermosensation, yet absent in animals lacking neurons responsible for low-threshold touch sensation. We further found that the mechanical response rests on a properly functioning DEG/ENaC ion channel. Deletion of its MEC-4 subunit abolishes the response. The evidence for a mechanical nature of the response allowed us to maximize mechanical stimulation by pulsing the stimulus at specific pulse repetition frequencies (PRFs). The optimal range of PRFs aligned with that used for US neuromodulation in large mammals including humans, and is consistent with the prediction of a recent molecular model of mechanosensation. Thus, the mechanical forces associated with US are capable of activating mechanosensitive ion channels in a freely behaving animal. The mechanical nature of the effect proposes a specific pulsing protocol to activate neurons that possess mechanosensitive properties in the peripheral and central nervous systems of animals and humans.