Electrocatalysts capable of working efficiently in acidic media for the oxygen evolution reaction (OER) are highly demanded for the large-scale utilization of proton exchange membrane (PEM) water electrolysis. This study focuses on the design and fabrication of cation/oxygen vacancy-enriched RuO₂ catalysts to investigate the impact of defect types on the OER activity and stability of RuO₂. The comprehensive blend of experimental and theoretical approaches elucidates that the presence of Ru vacancies in Ru_1–xO₂ modulates the d-band center and optimizes the adsorption energy of the OER intermediates, thereby augmenting the intrinsic OER activity. Conversely, the presence of oxygen vacancies in RuO_2-x diminishes the strength of Ru–O bonds, suppressing the involvement of the lattice oxygen oxidation mechanism (LOM) and Ru dissolution, consequently enhancing long-term stability. Notably, Ru_1–xO₂ exhibits the lowest overpotential of 212 mV at 10 mA cm_geo^–2, while RuO_2–x demonstrates superior stability, enduring 400 h under 10 mA cm_geo^–2, surpassing many catalysts for acidic OER in the literature. Our findings demonstrate that defect engineering is a promising strategy to achieve electrocatalysts with super catalytic performance in acid media for water electrolysis.