Developing efficient nonprecious metal catalysts for NO reduction using CO under O2-containing conditions has always been the focus of attention. In this study, the asymmetric Mn-Ov-Ce structure was constructed on the Mn-Ce catalyst via a coprecipitation strategy. The optimized Mn0.2Ce0.8O2 catalyst exhibited superior catalytic performance, achieving 90% NO conversion and 95% N2 selectivity at 260 °C under 5% O2. Characterizations and theoretical calculations revealed that the asymmetric Mn-Ov-Ce configuration promoted electron delivery between Mn and neighboring Ce, facilitating the generation of dynamic Ov. Furthermore, in situ DRIFTS and DFT calculations demonstrated that the incorporated Mn was favorable to a faster consumption of intermediates and the dynamic replenishment of Ov on the CeO2 surface, thus promoting the catalytic performance. This study provides an efficient scheme for designing high-efficiency performance Ce-based catalysts by tuning the electronic structure of CeO2 for NO reduction by CO under the O2-containing conditions.