Abstract The development of low ruthenium (Ru)‐based anodes with high activity and durability is crucial and still a challenge for proton exchange membrane water electrolysis (PEMWE) systems at a low cost. Here, we synthesized a Ru cluster catalyst (Ru clusters /ZnCo 2 O 4 ) loaded on zinc (Zn)‐doped cobalt oxide spinel, where the presence of Zn atoms transforms the support (ZnCo 2 O 4 ) from a “fragile structure” to a “stable substrate” and indirectly stabilizes the Ru active center by optimizing the electronic environment of the Ru sites through electron transfer meanwhile, thereby achieving a balance between high activity and stability in acidic oxygen evolution reaction (OER). The prepared catalysts with a low overpotential (200 mV) and can operate stably for over 725 h at 10 mA cm −2 (with a decay rate of only 0.143 mV h −1 ). A PEMWE device uses Ru clusters /ZnCo 2 O 4 as the anodes operate stably for over 275 h at 200 mA cm −2 , demonstrating promising application potential. Theoretical calculations and experiments reveal Zn atoms can regulate the support electronic structure concurrently, endowing the catalysts with high activity and long lifetime. This strategy provides a new paradigm for the development of acidic OER catalysts: utilizing inert metals to regulate the supports, achieving dual breakthroughs in activity and stability.