Prussian blue analogs (PBAs) are effective precatalysts for the oxygen evolution reaction (OER); however, the underlying mechanism of their electrochemical activation is still not well elucidated. In this study, we designed and constructed PBA-based precatalysts to determine the electrochemical activation mechanism and achieve high-efficiency OER. The PBAs undergo in situ electrochemical transformation to form the corresponding metal (oxy)hydroxides (M(O)OH) as the true OER catalyst. More importantly, the hexacyanoferrate ligands undergo repetitive interfacial coordination/etching with/from M(O)OH during the activation process. The distinct mechanism could achieve in situ Fe doping and enable defect incorporation. The defect-enriched Fe-NiOOH derived from a well-designed NiHCF/Ni(OH)₂ precatalyst requires a low overpotential of 227 mV to reach a current density of 10 mA cm⁻² and works stably at 130 mA cm⁻² over 100 h. This study provides fundamental insights into the electrochemical activation mechanism for developing advanced precatalysts for OER.