The direct synthesis of dimethyl carbonate (DMC) from CO₂ and methanol is a potential green alternative to the current industrial methods using toxic chemicals. Although many CeO₂-based catalysts have been explored, the key structural factor affecting their DMC activity is still unclear. Herein, single-crystalline CeO₂ catalysts bearing distinct but well-defined Ce coordination structures were examined. We found that methanol is the key species being activated by surface Ce sites (cf. CO₂) to produce methyl carbonate (MC) and later DMC. The reactivity of surface methoxy species towards CO₂ varies considerably with its configuration determined by Ce coordination structures. The head-to-head terminal methoxy species converts CO₂ to MC faster than its atilt counterparts, resulting in a higher DMC activity. The bridging methoxy species is, however, too stable to react with CO₂. The established structure-activity relation here should also guide the design of CeO₂-based catalysts in other reactions involving methanol activation.