Manganese−copper spinel is a kind of efficient catalyst for NO reduction by CO; however, its unsatisfactory lowtemperature catalytic performance and poor N 2 selectivity limit its application. Here, peanut-shaped Cu 0.75 Mn 2.25 O 4 nano-hollow spinel (Cu 0.75 Mn 2.25 O 4 -NH) was prepared by a one-pot solvothermal method and applied in NO reduction by CO. The structure and physicochemical properties of catalysts were researched by comprehensive characterizations. Compared with Cu 0 . 7 5 Mn 2 . 2 5 O 4 nanoparticles (Cu 0 . 7 5 Mn 2 . 2 5 O 4 -NP), Cu 0.75 Mn 2.25 O 4 -NH displayed excellent low-temperature catalytic performance, achieving 90% NO conversion at 200 °C, and possessed a lower apparent activation energy (36.4 kJ•mol −1 ). Importantly, the unique nanostructure with more exposed active sites enhanced the redox properties and oxygen mobility of the Cu 0.75 Mn 2.25 O 4 -NH catalyst. In addition, a synergistic effect between different metal ions in the Cu 0.75 Mn 2.25 O 4 -NH catalyst promoted the formation of oxygen vacancies and more low-oxidation-state species, which were conducive to the N−O bond scission at low temperatures. Combining the in situ DRIFTS results and DFT calculations, the dispersed species of Cu y+ -O-Mn x+ could be reduced to the main reactive species of Cu (y−1)+ -□-Mn (x−1)+ . Moreover, the formation of oxygen vacancies optimized NO adsorption and activation ability, which improved the catalytic performance in NO reduction by CO.