Hybrid metal nanoparticles can allow separate reaction steps to occur in close proximity at different metal sites and accelerate catalysis. We synthesized iron-nickel hydroxide-platinum (transition metal-OH-Pt) nanoparticles with diameters below 5 nanometers and showed that they are highly efficient for carbon monoxide (CO) oxidation catalysis at room temperature. We characterized the composition and structure of the transition metal-OH-Pt interface and showed that Ni2+ plays a key role in stabilizing the interface against dehydration. Density functional theory and isotope-labeling experiments revealed that the OH groups at the Fe3+-OH-Pt interfaces readily react with CO adsorbed nearby to directly yield carbon dioxide (CO2) and simultaneously produce coordinatively unsaturated Fe sites for O-2 activation. The oxide-supported PtFeNi nanocatalyst rapidly and fully removed CO from humid air without decay in activity for 1 month.