The electrocatalysis for CO reduction is interesting for both fundamental understanding of the reaction mechanisms and deriving products of higher values for the electrochemical conversion of CO2. Hereby, we report on the development of three-dimensional (3D) Cu nanostructures as advanced electrocatalysts for CO reduction. By thermal oxidation of commercial Cu foams in air, CuO nanowires or porous structures were grown on the 3D frameworks of the foam, which were then reduced to Cu by applying a cathodic electrochemical potential. The derived 3D Cu nanostructures were demonstrated to be highly active and selective for the electroreduction of CO, achieving an improvement in CO reduction current density by a factor of 6 as compared to the 2D counterpart with similar surface roughness factors, 76% Faradaic efficiency (FE) of CO conversion, and >50% FE toward ethanol. The catalytic enhancement mechanisms were further discussed in terms of transport and surface structure effects.