<p>H₂ production from water splitting with the utilization of renewable energy has been deeply pursued, along with rapid energy consumption and environmental pollution due to fossil energy combustion. Proton exchange membrane water electrolysis (PEMWE) operating in an acidic electrolyte has exhibited promising potential owing to its superior current density and H₂ purity, etc. However, the large-scale application of PEMWE has been hindered by the sluggish kinetics and poor stability of the anodic oxygen evolution reaction (OER) electrocatalysts under acidic conditions. Although the noble Ru/Ir-based materials have been extensively applied for catalytic acid OER, the expensive Ir with rare earth abundance makes it crucial to optimize their performance and reduce reliance on Ir content for Ir-based materials, and Ru overoxidation/dissolution due to the intrinsic property of strong Ru–O covalency usually results in Ru collapse from materials. Hence, it is of vital importance to achieve the trade-off between activity, stability, and cost for laying the foundation for further actual industrial applications of the PEMWE system. In this review, we summarize the latest outstanding research on OER in acid electrolyte over Ru/Ir-based catalysts. We categorize and discuss various construction strategies of Ru/Ir-based catalysts, including doping of heteroatoms, the introduction of vacancy or lattice distortion, as well as the construction of single-atom catalysts (SACs), alloys, and heterojunctions. Furthermore, we delve into the structure-activity relationship and different reaction mechanisms supported by the analysis of <i>ex/in situ</i> characterizations and theoretical calculations. Eventually, we propose the challenges in the construction of Ru/Ir-based catalysts for the future development and industrial-scale application for highly active and stable OER in an acid electrolyte.</p>