The piezoelectric effect triggered by mechanical energy could establish an internal electric field to effectively modulate the separation behavior of carriers. Herein, a novel CdIn2S4/Bi2WO6 (CIS/BWO) piezo-photocatalyst for removing diclofenac (DCF) from water was constructed for the first time. Encouragingly, the photocatalytic degradation activity of CIS/BWO was effectively promoted through the piezoelectric effect. Specifically, 10% CIS/BWO exhibited promising DCF degradation performance under co-excitation of light irradiation and ultrasonic vibration, with a degradation efficiency of 99.9% within 40 min, much higher than that of pure photocatalysts (72.3%) and piezocatalysts (60.3%). Meanwhile, an in-depth study of the charge carrier separation mechanism of the CIS/BWO composite under the piezo-photo synergy condition was proposed. Both the built-in electric field induced by the piezoelectric effect in BWO and the Z-scheme transfer path of the CIS/BWO heterojunction are beneficial to interfacial charge transfer. Moreover, the Z-scheme mechanism was further demonstrated by trapping experiments and the electron spin resonance (ESR) technique. Finally, the corresponding intermediates of DCF over CIS/BWO composites and possible degradation pathways were also investigated by DFT calculations and liquid chromatography-mass spectrometry.