Ca-Zn-Al oxide was prepared by co-precipitation method and the effect of preparation conditions on its catalytic performance was investigated. The Ca-Zn-Al oxide exhibited an excellent catalytic activity and stability for one-pot synthesis of dimethyl carbonate (DMC) from urea, 1,2-propylene glycol (PG), and methanol. XRD characterization and activity evaluation results indicated that new crystalline phases Ca3Al4ZnO10 and ZnAl2O4 could create a synergistic effect with CaO and ZnO, being responsible for the excellent catalytic performance of Ca-Zn-Al oxide. Response surface methodology (RSM) was used to investigate the effect of operating variables and to optimize conditions for the first-step reaction of PG and urea to propylene carbonate. Then the effect of reaction conditions for the transesterification of propylene carbonate with methanol to DMC was also investigated. As a result, a DMC yield of 84.7% was obtained under the appropriate reaction conditions. The Ca-Zn-Al oxide could be reused for four times without a significant change in its catalytic activity.