Enhancing the stability of Pt-based electrocatalysts for the sluggish cathodic oxygen reduction reaction (ORR) is critical for proton exchange membrane fuel cells (PEMFCs). Herein, high-entropy intermetallic (HEI) L12-Pt(FeCoNiCuZn)3 is designed for durable ORR catalysis. Benefiting from the unique HEI structure and the enhanced intermetallic phase stability, Pt(FeCoNiCuZn)3/C nanoparticles demonstrate significantly improved stability over Pt/C and PtCu3/C catalysts. The Pt(FeCoNiCuZn)3/C exhibits a negligible decay of the half-wave potential during 30,000 potential cycles from 0.6 to 1.0 V, whereas Pt/C and PtCu3/C are negatively shifted by 46 and 36 mV, respectively. Even after 10,000 cycles at potential up to 1.5 V, the mass activity of Pt(FeCoNiCuZn)3/C still shows ∼70% retention. As evidenced by the structural characterizations, the HEI structure of Pt(FeCoNiCuZn)3/C is well maintained, while PtCu3/C nanoparticles undergo severe Cu leaching and particle growth. In addition, when assembled Pt(FeCoNiCuZn)3/C as the cathode in high-temperature PEMFC of 160 °C, the H2-O2 fuel cell delivers almost no degradation even after operating for 150 h, demonstrating the potential for fuel cell applications. This work provides a facile design strategy for the development of high-performance ultrastable electrocatalysts.