This work reported the adsorption and reaction performance of FeOx supported subnanometer cluster and single‐atom Ir catalysts for the oxidation of CO at low temperature. By varying the pretreatment temperature and Ir loading, the single‐atom and subnanometer cluster Ir catalysts were obtained. The Ir subnanometer clusters exhibited higher activity for the oxidation of CO with or without the presence of H2 than the single‐atom counterpart. By using adsorption microcalorimetry and in situ infrared spectroscopy measurements, it was found that the Ir subnanometer clusters not only promoted the adsorption and reaction of CO and O2 but also facilitated the formation of OH species from reaction between H2 and O2, thus opening a new reaction pathway between CO and OH species to produce CO2 compared with that between CO and O species on the single‐atom counterpart. © 2017 American Institute of Chemical Engineers AIChE J, 63: 4003–4012, 2017