We report the competitive adsorption of CO, ethylene and acetate on a Pd–Au (100) surface in the reaction system of vinyl acetate synthesis with DFT method. The effect of CO on the catalytic performance of Pd–Au in the vinyl acetate system was also studied. Moreover, the method of reducing the content of CO in the industrial process and the reaction path of CO on the Pd–Au catalyst was investigated. Furthermore, the effect of CO on the acetoxylation of ethylene to vinyl acetate was reflected in two aspects. Firstly, the adsorption of CO on a Pd atom is more stable than that of ethylene, in which the adsorption of ethylene is blocked and the catalytic activity of the Pd–Au alloy decreases. Secondly, the Pd–Au alloy can catalyze the CO oxidation reaction.