The lack of efficient catalysts with a wide working temperature window and vital O2 and SO2 resistance for selective catalytic reduction of NO by CO (CO-SCR) largely hinders its implementation. Here a novel Ir-based catalyst with only 1 wt% Ir loading is reported for efficient CO-SCR. In this catalyst, contiguous Ir atoms are isolated into single atoms, and Ir-W intermetallic nanoparticles are formed, which are supported on ordered mesoporous SiO2 (KIT-6). Notably, this catalyst enabled complete NO conversion to N2 at 250°C in the presence of 1% O2 and had a wide temperature window (250–400°C), outperforming the comparison samples with Ir isolated-single-atomic-sites and Ir nanoparticles, respectively. Also, it possessed a high SO2 tolerance. Both experimental results and theoretical calculations reveal that single Ir atoms are negatively charged, dramatically enhancing the NO dissociation, while the Ir-W intermetallic nanoparticles accelerate the reduction of the N2O and NO2 intermediates by CO.