Three-dimensionally ordered macroporous (3DOM) Mn2O3-supported AuPdy alloy (xAuPdy/3DOM Mn2O3; x=1.0–3.8wt%; Pd/Au molar ratio : y=1.85, 1.92) catalysts were prepared using the polymethyl methacrylate-templating and polyvinyl alcohol-protected reduction methods, respectively. Physicochemical properties of the samples were characterized by means of numerous techniques, and their catalytic activities were evaluated for toluene oxidation. It is found that the AuPdy alloy nanoparticles (NPs) with an particle size of 2–4nm were uniformly dispersed on the surface of 3DOM Mn2O3, and the 3.8AuPd1.92/3DOM Mn2O3 sample performed the best: the temperature at 90% toluene conversion was 162°C at 40,000mL/(gh). Furthermore, the 3.8AuPd1.92/3DOM Mn2O3 sample was highly active even after calcination at 700°C. The introduction of water vapor to the feedstock induced a positive effect on toluene oxidation over 3.8AuPd1.92/3DOM Mn2O3, but a negative effect over 1.9Au/3DOM Mn2O3 or 1.9Pd/3DOM Mn2O3. The excellent catalytic activity, thermal stability, and water resistance of 3.8AuPd1.92/3DOM Mn2O3 were associated with its good activation adsorption of oxygen on AuPd1.92 NPs and strong interaction between noble metal NPs and 3DOM Mn2O3. The 3DOM Mn2O3-supported AuPdy alloy NPs are promising industrial catalysts for efficient removal of volatile organic compounds.