The search for highly active catalysts with low-Pt content to advance the commercialization of fuel cells is continuing to receive ample attention. Herein, we report that by doping a single Pt atom into Au₂₅ to form Pt₁Au₂₄ nanoclusters, the electrocatalytic activity for the direct formic acid oxidation (FAO) to carbon dioxide is enhanced significantly. The mass activity of Pt₁Au₂₄ (3.7 A mg_Pt+Au⁻¹) is nearly 12 and 34 times greater than that of Pt nanoclusters and the commercial Pt/C catalyst, respectively. Density functional theory (DFT) calculations and potential-dependent thermodynamic analyses provide fundamental insights into the reaction mechanism illustrating that FAO proceeds through the carboxyl (COOH) intermediate on Pt₁Au₂₄. The present study not only develops a novel class of single-Pt atom doped Au nanocluster electrocatalysts for fuel cells with high utilization of Pt, but also provides insight into the mechanism of FAO on Pt-doped Au nanoclusters. Moreover, this study begins to shed light on the structure-activity relationship and helps to provide a strategy to design new catalysts by tuning their catalytic properties at the atomic level.