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As a non-noble-metal catalyst, CuO has great potential in the catalytic combustion of CO and CH4. In this work, the influence of loading active copper components onto perovskites and essential operating parameters in flame aerosol synthesis has been experimentally and theoretically investigated to optimize the catalytic efficiency for the complete oxidation of lean CO and CH4. Herein, the CuO–SrTiO3nanocatalysts are one-step-synthesized by flame spray pyrolysis with varied copper loadings and precursor feeding rates. The sample under the precursor flow rate of 3 mL/min and the CuO loading of 15 mol % demonstrates optimal catalytic performance. It is primarily attributed to the excellent low-temperature reducibility and improved activity of copper species originated by CuO quantum dots and metal–support interaction. Besides, SrTiO3perovskite as a support can effectively inhibit the sintering of CuO quantum dots at high temperatures, which is responsible for the excellent sintering and water deactivation resistances.