Converting CO into CO, CH, and other hydrocarbons using solar energy presents a viable approach for addressing energy shortages. In this study, photocatalysts with S-deficient WO/ZnInS (WO/V-ZIS) S-scheme heterojunctions have been successfully synthesized. Under UV-vis light irradiation, 20 %WO/V-ZIS demonstrated significantly improved CO reduction activity and CH selectivity. Detailed characterization and density functional theory (DFT) calculations reveal that the enhanced performance is due to the synergistic optimization of the S-scheme heterojunction and sulfur vacancies (V) for CO reduction. The presence of V aids in the adsorption and activation of CO and enhances the separation of charge carriers. The 2D/2D S-scheme heterostructure assembled with WO nanosheets not only accelerates the migration and separation of photoexcited charge carriers but also improves the adsorption of HO and the formation of V, thereby increasing the adsorption and activation of CO and facilitating the protonation of CO* to produce CH. This study clarifies the synergistic effect of V and S-scheme heterostructures in improving photocatalytic performance, offering valuable insights into the photoactivation process of CO at V in S-scheme heterojunctions.