It　is　important　to　develop　an　efficient　noble-metal-based　catalyst　that　has　a　wide　work　temperature　window　and　good　stability　for　CO　preferential　oxidation　in　H2　(CO-PROX),　a　key　step　to　purify　industrial　hydrogen　resource.　Herein,　a　catalyst　of　Fe-substituted　hexaaluminate-supported　Ir　nanoparticles　with　a　mean　size　of　∼1.4　nm　(Ir/BaFeAl11O19)　is　synthesized.　It　can　exhibit　total　CO　conversion　for　the　CO-PROX　reaction　in　an　unprecedented　temperature　range　from　20　to　200　°C,　high　stability,　and　good　resistance　to　CO2　and　H2O　in　a　simulated　practical　atmosphere.　Detailed　characterizations　coupled　with　density　functional　theory　(DFT)　calculations　show　that　the　interaction　between　Ir　species　and　framework　Fe　cations　in　mirror　planes　of　hexaaluminate　promotes　the　formation　of　a　certain　amount　(8%)　of　Fe2+　species　for　low-temperature　CO　oxidation,　while　the　Ir　species　interacting　with　these　Fe2+　provide　moderate　CO　bond　strength　that　is　critical　to　maintaining　the　preferential　oxidation　of　CO　rather　than　H2　at　high　temperatures.　©　2021　American　Chemical　Society