The current work provide a new understanding on the active site of CuMnOx catalysts and thus offer a new perspective in the development of highly effective and low cost CuMnOx catalysts for heterogeneous catalytic oxidation reactions. A series of dual-component copper-manganese multi-oxide catalysts (CuMnOx) have been successfully synthesized using a surfactant assisted hydrolysis-hydrothermal method and studied by XRD, N2 adsorption–desorption test, ICP-AES, SEM, Aberration-corrected HADDF-STEM, HRTEM, FT-IR, Raman, XPS, H2-TPR. These CuMnOx catalysts were found to be composed with uniform CuO-Mn2O3 oxide pair structure, in which highly isolated/dispersed CuO species are anchored in the framework of Mn2O3. It was found that the speciation in these CuMnOx catalysts presents a shift from highly isolated or even single Cu2+ oxide species (Cu2+Ox) to CuO nanoclusters and CuO microcrystalline with increasing Cu content. In CO oxidation reaction, which was employed to probe the structure of the CuO-Mn2O3 oxide pairs in these CuMnOx catalysts, the Cu-O-Mn sites in those CuMnOx catalysts with highly isolated or highly dispersed CuO species were found to be highly active. For CuO-Mn2O3 oxide pair catalysts, the highly isolated/dispersed CuO species in Mn2O3 framework is essential to achieve high activity.