Alloying techniques show genuine potential to develop more effective catalysts than Pt for oxygen reduction reaction (ORR), which is the key challenge in many important electrochemical energy conversion and storage devices, such as fuel cells and metal-air batteries. Tremendous efforts have been made to improve ORR activity by designing bimetallic nanocatalysts, which have been limited to only alloys of platinum and transition metals (TMs). The Pt-TM alloys suffer from critical durability in acid-media fuel cells. Here a new class of mesostructured Pt-Al catalysts is reported, consisting of atomic-layer-thick Pt skin and Pt3Al or Pt5Al intermetallic compound skeletons for the enhanced ORR performance. As a result of strong Pt-Al bonds that inhibit the evolution of Pt skin and produce ligand and compressive strain effects, the Pt3Al and Pt5Al mesoporous catalysts are exceptionally durable and approximate to 6.3- and approximate to 5.0-fold more active than the state-of-the-art Pt/C catalyst at 0.90 V, respectively. The high performance makes them promising candidates as cathode nanocatalysts in next-generation fuel cells.