Herein, Cu–Mn catalysts were used to study the catalytic oxidation system of toluene, revealing the optimal preparation conditions for catalytic oxidation of toluene and the effects of other factors on catalytic performance (oxygen concentration, toluene concentration, temperature, humidity, space velocity). The as‐synthesized Cu2Mn1Ox exhibited the best catalytic activity and stability. The BET, XRD, and O2‐TPD results indicated that the synthesized Cu2Mn1 catalyst can effectively form the Cu1.4Mn1.6O4 phase at the optimal calcination temperature (500–600°C) and accelerate the toluene degradation at 220°C. Although water vapor can promote the progress of catalytic reactions, excessive water vapor tends to form competitive adsorption at active sites, inhibiting the progress of catalytic reactions. In addition, oxygen concentration plays a key role in catalytic reactions. Based on the results, it was found that at lower oxygen concentrations or higher toluene concentrations, the catalyst was easy to react with toluene to generate Cu and MnO, resulting in catalyst deactivation.