Piezocatalysis is capable of harnessing mechanical energy for environmental remediation, which is regarded as a green and promising technology to be exploited. Piezoceramics are struggling to be used as highly efficient piezocatalysts due to their grain size reaching tens of micrometers usually. Herein, a feasible and straightforward method is proposed to turn piezoceramic powders into highly efficient piezocatalysts by integrating size optimization and oxygen vacancy modulation. This strategy is validated by treating lead-free SrBaNbO (SBN) piezoceramic powders with high-energy ball-milling (hBM). The rate constant k value of 46.95 × 10 min for rhodamine B (RhB) piezocatalytic degradation of SBN-hBM-12h is almost 18 times higher than that of pristine SBN. Besides, the SBN-hBM-12 h catalyst performed superior antibacterial properties against Escherichia coli. The enhanced piezocatalytic efficiency is attributed to the introduced abundant oxygen vacancies absorbing and activating O into reactive oxygen species. Well-modulated oxygen vacancy concentration can effectively accelerate the generation and separation of free carriers. However, the excess oxygen vacancies in SBN render the weakened piezoresponse thus suppressing the piezocatalytic activity. This study elucidates the critical role of oxygen vacancies in piezocatalysis and provides insights into the development of efficient piezocatalysts.