Developing low-iridium electrocatalysts combined with high efficiency and longevity for oxygen evolution reaction (OER) in proton exchange membrane (PEM) water electrolysis remains challenging in the hydrogen economy. Here, an anodic electro-oxidation approach is reported to fabricate iridium (Ir) dope MnO2 gas diffusion electrodes, which exhibited remarkable stability of over 1650 h at 100 mA cm−2 with a record-high stability number of 2.9 × 108 by considering Ir leaching. The optimized catalyst with a low Ir loading of ≈0.3 mg cm−2 achieved stable operation at 1.0 A cm−2 in the PEM electrolyzer. The investigation reveals that the generation of high-valence Ir within MnO2 optimizes oxygen desorption and thereby boosts activity. Furthermore, MnO2 provides a platform that enables the oxidation and deposition of leached ions, initiating a self-healing mechanism that extends the operational lifetime of catalyst. This paves an effective way toward addressing the dissolution issues encountered by OER catalysts in acidic electrolytes.