Manganese oxide (MnOx) supported on CeO2 nanocubes (MnOx/CeO2) were synthesized and tested for the catalytic combustion of chlorobenzene (CB), which was taken as a model compound of chlorinated volatile organic compounds (CVOCs). The catalytic activity tests demonstrated that MnOx/CeO2 nanocube catalysts exhibited a catalytic activity significantly better than that of bare CeO2 nanocubes, indicating MnOx plays a significant role for CB oxidation. To illustrate the effect of MnOx on the CeO2 nanocubes, experimental and theoretical methods such as density functional theory (DFT) calculations were carried out. Experimental characterization testified that the introduction of MnOx to CeO2 nanocubes brought the facile reduction of cerium species, larger amount of Oα species and oxygen vacancies, which lead to the enhanced catalytic performance of MnOx/CeO2 nanocube. Furthermore, DFT calculations clearly validated that MnOx/CeO2 (100) models could form the oxygen vacancies more easily, and CB molecules were preferentially adsorbed on the MnOx/CeO2 (100) models than on the CeO2 (100) models, which facilitated the easier formation of C-O* bond; this facile bond formation enabled faster CB decomposition into COx, thereby a higher CB conversion on the MnOx/CeO2 (100) could be found. Therefore, the vital role of MnOx can be successfully elucidated by both experimental and theoretical methods. Hence, this finding can be utilized for enhanced catalytic performance of CeO2 nanocube catalysts for the CVOCs elimination.