Abstract: As one of the common gaseous pollutants, CO has seriously affected human healthy life andgreen economic development. Extensive research has shown that the supported metal oxide catalysts canperform efficient catalytic oxidation of CO. However, how to obtain catalysts with high CO oxidationperformance from numerous oxides and to reveal the key factors impacting CO oxidation activity frommicroscopic aspects have been the topical concerns of researchers. In this paper, we investigated theCO oxidation reactions on the surface of a series of supported transition metal oxide MxOyHz / TiO2 cata⁃lysts using density functional theory (DFT) calculations, and analyzed the key factors influencing theCO oxidation reactions conducted on the catalyst surface. Then the CO oxidation activity of partiallysupported oxides was calculated and predicted. The results showed that the adsorption energy (Eads) ofCO molecules on the catalyst surface and the oxygen vacancy formation energy (Eov) of the active sitejointly determine the CO oxidation activity of the catalyst. The CuO/ TiO2 catalyst exhibited the highestCO catalytic oxidation activity; VO3 H, CrOH3, ZrO2, and WO3 / TiO2 displayed the lowest activity;the remaining catalysts were intermediate in activity. Then activity testing experiments were carried outand the results were found to be consistent with the DFT calculations.