The development of Ru-based acidic oxygen evolution reaction (OER) catalysts is crucial for enhancing the efficiency of electric-driven water electrolysis, yet their stability remains constrained by the susceptibility of Ru active centers to dissolution and over-oxidation. In this work, a Ru/Ta2O5(V) catalyst with abundant 5d electron buffering interfaces was fabricated by an oxide defect separation strategy. Through strong metal–support interactions to modulate the electronic structure of Ru active sites, we effectively balance the trade-off between catalytic activity and stability. The optimized Ru/Ta2O5(V) demonstrates a low overpotential of 272 mV at 10 mA cm−2 and maintains stable operation for 190 hours with an ultralow voltage increment rate. In situ infrared spectroscopy and X-ray photoelectron spectroscopy reveal that the anchoring of Ru on the support surface modulates the electron cloud density around Ru sites via Ta 5d electrons, which not only optimizes the reaction pathway but also significantly improves the corrosion resistance in acidic environments, effectively mitigating the dissolution and excessive oxidation of active sites during the OER process. This work proposes a novel structural design strategy for achieving stable acidic OER catalysis through rational Ru immobilization on inert supports.