Catalytic total oxidation of 1,2-dichloroethane (DCE) on CeO2 and VOx/CeO2 catalysts is investigated via various isotopic tracer techniques, including kinetic isotope effect (KIEs) measurements, in situ diffuse reflection infrared Fourier transform spectroscopy (DRIFT) of deuterated 1,2-dichloroethane oxidation, H/D exchange of surface hydroxyl groups, temperature-programmed isotopic exchange (TPIE) and 18O2 isotope labeling experiments. The activation and dissociation of CCl bonds is determined to be the first step of DCE oxidation, and oxygen vacancies are identified as the main active sites by KIEs and density functional theory (DFT) calculations. For VOx/CeO2 catalysts, surface lattice oxygen is found to directly involve in oxidation of DCE via the formation of intermediate species of partial oxidation such as aldehyde species or CO, which are then totally oxidized into CO2 by the surface peroxide species. The occurrence of HCl is attributed to the reaction of surface hydroxyl groups with the dissociated Cl adsorbed on oxygen vacancies, whereas the rapid replenishment of the consumed OH is crucial for maintaining a better stability.