Solar-powered water splitting is a dream reaction for constructing an artificial photosynthetic system for producing solar fuels. Natural photosystem II is a prototype template for research on artificial solar energy conversion by oxidizing water into molecular oxygen and supplying four electrons for fuel production. Although a range of synthetic molecular water oxidation catalysts have been developed, the understanding of O−O bond formation in this multielectron and multiproton catalytic process is limited, and thus water oxidation is still a big challenge. Herein, we report a trinuclear copper cluster that displays outstanding reactivity toward catalytic water oxidation inspired by multicopper oxidases (MCOs), which provides efficient catalytic four-electron reduction of O 2 to water. This synthetic mimic exhibits a turnover frequency of 20000 s −1 in sodium bicarbonate solution, which is about 150 and 15 times higher than that of the mononuclear Cu catalyst (F−N 2 O 2 Cu, 131.6 s −1 ) and binuclear Cu 2 complex (HappCu 2 , 1375 s −1 ), respectively. This work shows that the cooperation between multiple metals is an effective strategy to regulate the formation of O−O bond in water oxidation catalysis.