The development of highly efficient and stable Pd-based catalysts is crucial to improve their sluggish oxygen reduction reaction (ORR) kinetics in acid media. To improve ORR activity and utilization efficiency of Pd, an ideal catalyst should have ORR-favorable chemical environment, optimized geometric structure, and long periods of operation. In this work, we first synthesize a novel trimetallic Au@PdPb core-shell catalyst consisting of PdPb alloy nano-layers grown on the surface of ultrathin Au nanowires (NWs) by a two-step water-bath method. The Au@PdPb NWs have the merits of anisotropic one-dimensional nanostructure, high utilization efficiency of Pd atoms and doping of Pb atoms. Because of the structural and multiple compositional advantages, Au@PdPb NWs exhibit remarkably enhanced ORR activity with a high haIf-wave potential (0.827 V), much better than those of commercial Pd black (0.788 V) and bimetallic Au@Pd NWs (0.803 V). Moreover, Au@PdPb NWs display better electrocatalytic stability for the ORR than those of Pd black and Au@Pd NWs. This study demonstrates the validity of our approach for deriving highly ORR-active Pd-based catalysts by modifying their structure and composition.