Inert substrate supported Ir catalyst for room-temperature oxidation of formaldehyde has never been reported so far. Here, a novel Ir-based catalyst supported on commercial γ-Al2O3 (IrAl-CD), which was synthesized via a modified colloid-deposition method, can realize complete conversion of HCHO at 20 °C for the first time. It exhibits a two-fold higher specific rate than IrAl-DP prepared by a conventional deposition-precipitation method. Detailed characterizations demonstrate that the positive Ir species bonded with OH groups on IrAl-DP make HCHO oxidation follow a reaction pathway between OH and formate intermediates. In contrast, the fairly high content of metallic Ir0 species on IrAl-CD facilitates the direct dehydrogenation of HCHO to form the dominant intermediates of CO, which are easily oxidized with a lower activation energy. Consequently, the electronic state of Ir determines the extremely high performance even supporting on inert substrate and the reaction mechanism for HCHO oxidation at ambient temperature.