Abstracttext. The sluggish kinetics of the hydrogen oxidation reaction (HOR) in alkaline conditions continue to pose a significant challenge for the practical implementation of anion‐exchange membrane fuel cells. Developing single‐atom catalysts can accelerate the pace of new HOR catalyst discovery for highly cost‐effective and active HOR performance. However, single‐atom catalysts (SACs) for the alkaline HOR have rarely been reported, and fundamental studies on the rational design of SACs are still required. Herein, we report the design of Ru SAC supported on the ordered mesoporous tungsten carbide (Ru SA/WC1‐x) via in situ high‐temperature annealing strategy. The resulting Ru SA/WC1‐x catalyst exhibits remarkably enhanced HOR performance in alkaline media, a level of activity that could not be achieved with carbon‐supported Ru SAC. Electrochemical results and density functional theory demonstrate that promoting the hydroxyl adsorption on Ru SA/WC1‐x interfaces, which is derived from the low potential of zero charge of WC1‐x support, has significant effect on enhancing the HOR performance of SACs. This enhancement leads to 5.8 and 60.1 times higher Ru mass activity of Ru SA/WC1‐x than Ru nanoparticles on carbon and Ru SA on N‐doped carbon, respectively. This work provides new insights into the design of highly active SACs for alkaline HOR.This article is protected by copyright. All rights reserved