Reactive oxygen species (ROS) have been growing as an emerging “hot” topic in antimicrobial applications. However, optimizing antimicrobial activity by enhancing ROS generation remains a formidable challenge. Here, using bassanite as a proof of concept, the facet engineering of bassanite matrix can enhance the ROS generation efficiency via tuning the d‐band center of Cu atom is proposed. Theoretical calculation and experimental investigations reveal that the d‐band center of Cu atoms is significantly shifted upward when Cu doped into the (204) facet of bassanite compared to the (400) facet. A higher d‐band center facilitates adsorption and activation between Cu and O2 through the formation of stronger d‐π* orbital hybridization, resulting in increased ROS production. Through engineering, the material exhibits better antimicrobial activity when Cu doped into the (204) facet, which presents a clear potential in construction materials and personal protection. This work shed light on designing new materials with high antimicrobial activity and the application of facet engineering.