AbstractStrongly oxidizing ·OH can non‐selectively degrade various organic pollutants, but how to selectively generate ·OH is a great challenge. In this study, the directed generation of ·OH was achieved based on Ni–Ca metastable–nonmetastable bimetallic sites, Ni2+/Ni3+ valence cycling provided electrons for ·OH generation induced by the non‐variable Ca‐based sites, which constructed a nearly 100% selective generation pathway of ·OH (O3 → HO3/HO2 → OH). The antibiotic pefloxacin could be completely removed in 15 min, and the COD removal efficiency for other hard‐to‐degrade pollutants such as oxalic acid and chlorobenzoic acid could reach more than 90%. Ni doping significantly increased the oxygen vacancy and Lewis acid content, and DFT calculations showed that Ni–Ca dual‐site had a lower reaction energy barrier and the complexed hydroxyl radical intermediate *OO had a higher spin density (−0.6), which was more favorable for the generation of ·OH. Therefore, this study provides new ideas for efficient treatment of actual wastewater.