CO esterification to dimethyl carbonate (DMC) is an attractive route, although the catalyst is the main problem restricting the industrialization of this route. Supported palladium catalysts have been often used for this route. However, the effect of the support is not always clear. In this work, we firstly introduced three metal–organic frameworks (MOFs) materials as catalyst supports, namely UiO-66, MIL-101 and MOF-5, and studied the effect of Lewis acid sites in the MOFs supports on the catalytic activity and selectivity for CO esterification to DMC. Interestingly, the Pd(II)/UiO-66 catalyst exhibits superior catalytic performance to the other catalysts, with 87.9% CO conversion and 98.5% DMC selectivity due to the abundant Lewis acid sites in UiO-66. It was proven that UiO-66 with more defects would have a large number of Lewis acid sites, and the catalytic performance was positively correlated with the number of Lewis acid sites in MOFs supports, which can be demonstrated by characterization by NH3-TPD, pyridine-IR, XPS and in situ DRIRS. The current work not only revealed the relationship between the Lewis acidity of the support and catalytic performance, but also promotes the development of practical catalysts for CO esterification to DMC.