CO₂ hydrogenation over Cu-based catalysts has the potential to enable green methanol synthesis. A unique reduction-exsolution strategy based on CuAl₂O₄ spinel is proposed to significantly enhance the structural tunability and catalytic performance of Cu-based catalysts. In-situ characterization demonstrates that this strategy can synthesize catalysts featuring uniform dispersed Cu particles, abundant surface Cu⁺ species and oxygen vacancies, and superior methanol selectivity and yields. By exploiting CuAl₂O₄ as the precursor, this reduction-exsolution strategy also enriches Cu/oxide interfacial sites, on which the methanol yield of optimized ZnO/CuAl₂O₄ catalyst has surpassed that of a commercial Cu/ZnO/Al₂O₃ catalyst. Detailed structure-performance correlations highlight the broad applicability of this design principle, offering new avenues for developing efficient Cu-based catalysts.