A series of CuO-based catalysts supported on the α-MnO2 nanowire were facilely synthesized and employed as the CO oxidation catalysts. The achieved catalysts were systematically characterized by XRD, SEM, EDS-mapping, XPS and H2-TPR. The catalytic performances toward CO oxidation had been carefully evaluated over these CuO-based catalysts. The effects of different loading methods, calcination temperatures and CuO loading on the low temperature catalytic activity of the catalyst were investigated and compared with the traditional commercial MnO2 catalyst with a block structure. It was found that the slenderness ratio of a CuO/α-MnO2 nanowire catalyst decreases with the increase in CuO loading capacity. The results showed that when CuO loading was 3 wt%, calcination temperature was 200 °C and the catalyst that was supported by the deposition precipitation method had the highest catalytic activity. Besides, the α-MnO2 nanowire-supported catalysts with excellent redox properties displayed much better catalytic performances than the commercial MnO2-supported catalyst. In conclusion, the CuO-based catalysts that are supported by α-MnO2 nanowires are considered as a series of promising CO oxidation catalysts.