The gas-phase carbonylation of dimethoxymethane (DMM) to form methyl methoxyacetate (MMAc) can be catalyzed by acid zeolites. This reaction is a critical step in the synthesis of monoethylene glycol (MEG), a widely used chemical, from synthesis gas. The mechanism of DMM carbonylation occurring on H−MFI and H−FAU zeolites has been investigated using density functional theory. We find that the reaction involves three steps: initiation via reaction of zeolite protons with DMM to form methoxymethoxy species, carbonylation of the resulting species, and subsequent methoxylation of the resulting acyl species. Both the carbonylation and methoxylation processes proceed via carbocationic transition states that are stabilized by the framework O atoms of the zeolite. The activation barriers for carbonylation are similar in both zeolites, but the barriers for methoxylation differ significantly. Energy decomposition analysis indicates that a combination of the pore size and of the flexibility of the reactive species gives rise to the differences in reactivity between the zeolites. The effect of basis set superposition was assessed using a 6-311++G(3df,3pd) basis set. This effect depends strongly on the gas-phase molecules involved but very weakly on the zeolite framework, and its estimate can be transferred from one zeolite to another to reduce the computational expense of such simulations.