We reported herein the development of heterobimetallic NiFe molecular platform to understand NiFe synergistic effect in water oxidation catalysis. Compared to homonuclear bimetallic compounds (NiNi and FeFe), NiFe complex possesses more remarkable catalytic water oxidation performance. Mechanistic studies suggest that this remarkable difference is attributed to the fact that NiFe synergy can effectively promote O−O bond formation. The generated NiIII(μ‐O)FeIV=O is the key intermediate and O−O bond was formed via intramolecular oxyl‐oxo coupling between bridged O radical and terminal FeIV=O moiety. A family of structurally well‐defined bimetallic complexes (FeFe, NiFe, NiNi, ZnFe, NiZn) was used as a molecular platform to understand Ni/Fe cooperative water oxidation mechanism. The results disclosed that O−O bond formed via intramolecular oxyl‐oxo coupling between bridged O radical and terminal FeIV=O moiety in NiIII(μ‐O)FeIV=O species, which provides a helpful guidance for rational design of heterobimetallic catalysts.