CuO microspheres were constructed with self-assembled CuO nanosheets through a hydrothermal method. Then, CeO₂ nanoplatelets were decorated on the surface of CuO nanosheets to obtain inverse CeO₂/CuO catalysts. The catalysts were characterized by using XRD, SEM, HRTEM, XPS, Raman spectroscopy, and H₂-TPR techniques. It was found that the CeO₂/CuO inverse catalysts had a hierarchical structure and a much lower 100% CO conversion temperature than that of CuO microspheres. A model of the structure and catalytic effect based on the contact interface between CeO₂ and CuO is discussed. The two-dimensional CuO nanosheets and CeO₂ nanoplatelets were most favorable for the formation of long periphery at the CeO₂/CuO interface, therefore, enhanced catalytic activity was achieved.