Atomically dispersed catalysts have been shown highly active for preferential oxidation of carbon monoxide in the presence of excess hydrogen (PROX). However, their stability has been less than ideal. We show here that the introduction of a structural component to minimize diffusion of the active metal center can greatly improve the stability without compromising the activity. Using an Ir dinuclear heterogeneous catalyst (DHC) as a study platform, we identify two types of oxygen species, interfacial and bridge, that work in concert to enable both activity and stability. The work sheds important light on the synergistic effect between the active metal center and the supporting substrate and may find broad applications for the use of atomically dispersed catalysts.