The carbonylation of dimethyl ether (DME) to methyl acetate (MA) is one of the crucial steps in an indirect synthesis route of ethanol from syngas (CO+H-2). The H-MOR zeolite exhibits excellent activity and selectivity at mild conditions. However, the catalyst suffers rapid deactivation due to the carbonaceous deposits on Bronsted acid sites. In this study, the deactivation kinetics for the carbonylation of DME to MA on the H-MOR zeolite was investigated. Based on the fitting results and in situ FTIR analysis, a model taking into account the composition concentration was established. This deactivation kinetic model allows simulating the concentration of different compounds in the reaction medium with time on stream under different experimental conditions. In this model, coke is considered to be derived from DME and CO. Moreover, CO remarkably accelerates the coke formation, and the effect of its concentration on the deactivation rate is quantified. The establishment of deactivation kinetics will be conductive to elucidate the coke formation mechanism and optimize the process conditions.