Flame in situ synthesis is regarded as a facile technique to fabricate onedimensional (1D) nanomaterials with the advantages of simple operation, shorter duration, and scale production. This work reports the flame synthesis of transition metal (Ce,Fe)anchored CuO nanowires on a copper substrate for CO catalytic oxidation. Thermal compressive stresses encourage the CuO nanowires to grow vertically along the grain boundaries, and the metal oxides are nucleated and embedded along the nanowires due to pyrolysis. We examined the catalytic performance of the as-grown catalysts toward CO oxidation, and the results showed that the CeFe-Cu catalyst exhibits outstanding activity near full conversion at 180 °C. With a reaction rate per unit mass of 1.38 mol g cat −1 s −1 and activation energy of 43.54 kJ mol −1 , the high activity of the CeFe-Cu catalyst benefits from the synergistic effects of Ce-Fe incorporation. Furthermore, the CeFe-Cu catalyst displays stable cycling performance over five runs and excellent stability in isothermal long-term catalysis tests at 140 °C. Kinetic analysis gives the rate equations for CO oxidation over the Ce-Cu, Fe-Cu, and CeFe-Cu catalysts and reveals the influential role of chemisorbed CO and lattice oxygen in the reaction. The catalytic oxidation of CO undergoes two reduction−oxidation steps as corroborated by the Mars Van Krevelen (MVK) model, and oxygen vacancies are crucial to facilitating the deep oxidation of CO, as confirmed by XPS. Meanwhile, combined with in situ Raman analysis, a reasonable mechanism is proposed. This work provides a fast method of designing 1D hybrid nanostructures for the abatement of carbon monoxide from exhaust gas emissions.