Water splitting using renewable energy is widely recognized as a green and sustainable strategy toward deploying a future hydrogen economy. In this context, piezocatalysis, in which different catalytic reactions (e.g., water splitting) are activated by various forms of mechanical energy (e.g., vibration, water flow, and ultrasonication), is a promising approach. In the past decade, numerous piezoelectric nanomaterial-based catalysts have been developed, recently reaching hydrogen production rates of the order of mmol g−1 h−1, comparable with state-of-the-art photocatalysis. In this review, we provide an overview of the fundamental principles of piezocatalytic water splitting, including a comprehensive description of the developed piezocatalytic materials. We mainly focus on the critical factors that determine the performance of mechanically driven water splitting over piezoelectric nanomaterials. We conclude by highlighting the main unresolved challenges and outlining promising future research directions in this emerging field.