Piezocatalysis, the process of directly converting mechanical energy into chemical energy, has emerged as a promising alternative strategy for green H production. Nevertheless, conventional inorganic piezoelectric materials suffer from limited structural tailorability and small surface area, which greatly impedes their mechanically driven catalytic efficiency. Herein, we design and fabricate a novel UiO-66(Zr)-F metal-organic framework (MOF) nanosheet for piezocatalytic water splitting, with the highest H evolution rate reaching 178.5 μmol g within 5 h under ultrasonic vibration excitation (110 W, 40 kHz), far exceeding that of the original UiO-66 host. A reduced bandgap from 2.78 to 2.43 eV is achieved after introducing a fluorinated ligand. Piezoresponse force microscopy measurements demonstrate a much stronger piezoelectric response for UiO-66(Zr)-F, which may result from the polarity of the introduced fluorinated ligand. This work highlights the potential of MOF-based porous piezoelectric nanomaterials in harvesting mechanical energy to drive chemical reactions such as water splitting.