CO₂ hydrogenation to chemicals and fuels is a significant approach for achieving carbon neutrality. It is essential to rationally design the chemical structure and catalytic active sites towards the development of efficient catalysts. Here we show a Ce-CuZn catalyst with enriched Cu/Zn-O_V-Ce active sites fabricated through the atomic-level substitution of Cu and Zn into Ce-MOF precursor. The Ce-CuZn catalyst exhibits a high methanol selectivity of 71.1% and a space-time yield of methanol up to 400.3 g·kg_cat⁻¹·h⁻¹ with excellent stability for 170 h at 260 °C, comparable to that of the state-of-the-art CuZnAl catalysts. Controlled experiments and DFT calculations confirm that the incorporation of Cu and Zn into CeO₂ with abundant oxygen vacancies can facilitate H₂ dissociation energetically and thus improve CO₂ hydrogenation over the Ce-CuZn catalyst via formate intermediates. This work offers an atomic-level design strategy for constructing efficient multi-metal catalysts for methanol synthesis through precise control of active sites.