Sulfur (S) vacancies in metal sulfides are of interest in electrocatalysis and photoelectronics, but their effect on the generation of reactive oxygen species (ROS) during mechanical catalysis is unclear. This study investigates the impact of S-vacancies in defective bismuth sulfide (Bi2S3-x) on ROS production under ultrasonic irradiation and organic contaminant decomposition. S-vacancies disrupt the centrosymmetric structure of intrinsic Bi2S3, inducing piezoelectric effects and enhancing the electrical energy in Bi2S3-x. The positively charged S-vacancies in Bi2S3-x promote the separation of ultrasound-activated electron-hole pairs by capturing electrons. As a result, the optimal rate of H2O2 formation and the reaction rate constant for degrading Rhodamine B dye on Bi2S3-x are found to be 1.9 and 37 times higher, respectively, than those on Bi2S3 under ultrasonic irradiation. The nonzero catalytic efficiency in centrosymmetric Bi2S3 is due to the flexoelectric catalytic effect from nonuniform strain. These results guide the piezocatalyst design and elucidate mechanical catalysis mechanisms.