Generating different types of defects in heterogeneous catalysts for synergetic promotion of the reactivity and selectivity in catalytic reactions is highly challenging due to the lack of effective theoretical guidance. Herein, we demonstrate a facile strategy to introduce two types of defects into the CuO-ZnO model catalyst, namely oxygen vacancies (OVs) induced by H₂ partial reduction and localized amorphous regions (LARs) generated via the ball milling process. Using industrially important Rochow–Müller reaction as a representative, we found OVs predominantly improved the target product selectivity of dimethyldichlorosilane, while LARs significantly increased the conversion of reactant Si. The CuO-ZnO catalyst with optimized OVs and LARs contents achieved the best catalytic property. Theoretical calculation further revealed that LARs promote the generation of the Cu₃Si active phase, and OVs impact the electronic structure of the Cu₃Si active phase. This work provides a new understanding of the roles of different catalyst defects and a feasible way of engineering the catalyst structure for better catalytic performances.