Catalytic combustion has been widely applied to remove the trace combustible pollutants. However, the earth-abundant and high-performance nanocatalysts are still the main research focus on promoting catalytic efficiency. Herein, the Cu and Mn mixed oxides supported on TiO2 nanoparticles with various Cu and Mn molar contents synthesized via the flame spray pyrolysis (FSP) technique are utilized in the catalytic oxidation of lean CO and CH4. Initially, the Cu-Mn/TiO2 nanocatalysts are composed of spherical structures with a diameter of about 20 nm, whose specific surface area is between 60 and 90 m(2)/g. The Cu element is more evenly distributed on the TiO2 surface than the Mn element, owing to the distinctly different ion radii. Both the copper and manganese cations could incorporate into the TiO2 lattice, which generates oxygen vacancies and enhances the diffusion of oxygen ions, causing the transformation of the antanse to rutile phase. When the molar content of the Cu-Mn increases to less than 30 mol %, the temperature of its reduction peak keeps decreasing due to the hydrogen spillover effect. Moreover, the catalytic performances of the Cu-Mn/TiO2 with 12 mol % loading (12CMT) are all optimal during the low-temperature and the high-temperature stages, which are superior to the FSP-made copper manganese or copper titanium oxides. This is attributed to the small crystal particles, highly dispersed active components of CuOx and MnOx, and the higher ratios of Cu1-/Cu and Mn4+-O-ads Lewis acid-base pairs. In addition, the strong interaction between Cu-Mn components and rutile phase support can tremendously promote the activity of catalytic combustion. Under the simulated flue gas, the catalytic properties of 12CMT decreases in comparison with those of CO and CH4 mixed gas due to the introduction of CO2. Ultimately, the Cu-Mn/TiO2 samples exhibit the outstanding water resistance, thanks to the hydrophobization of the catalyst surface.