Tough bioadhesion has important implications in engineering and medicine but remains challenging to form and control. We report an ultrasound (US)-mediated strategy to achieve tough bioadhesion with controllability and fatigue resistance. Without chemical reaction, the US can amplify the adhesion energy and interfacial fatigue threshold between hydrogels and porcine skin by up to 100 and 10 times. Combined experiments and theoretical modeling suggest that the key mechanism is US-induced cavitation, which propels and immobilizes anchoring primers into tissues with mitigated barrier effects. Our strategy achieves spatial patterning of tough bioadhesion, on-demand detachment, and transdermal drug delivery. This work expands the material repertoire for tough bioadhesion and enables bioadhesive technologies with high-level controllability.