Significance The efficiency with which renewable fuels and feedstocks are synthesized from electrical sources is largely limited by the sluggish water oxidation reaction. We show that the optimal water oxidation catalyst could be achieved by systematically modulating the coordination of the Ir active sites using an in situ cryogenic–photochemical reduction synthesis method. We achieved a highly oxidized Ir single site (Ir ^+5.3 ) in the best atom utilization by single-atom catalysts on electrochemically stable supports. The origin of water oxidation activity in an Ir single-atom catalyst is revealed experimentally and theoretically. The concept and strategy of this work are expected to pioneer novel approaches to engineer single-atom catalysts.