Pt-based intermetallic alloys with high activity and stability are promising for accelerating the cathodic oxygen reduction reaction (ORR) and large-scale application of proton exchange membrane fuel cells. So far, facile synthesis of Pt-based alloys in less time is desirable but still challenging. Herein, based on the traditional wet impregnation method, facile in situ reduction of H2PtCl6 and alloying with a hybrid nanostructure mainly doped with Fe single atoms as well as small amounts of Fe-based nanoparticles and oxides were developed to fabricate highly dispersed PtFe nanoparticles loaded on a mesoporous Fe–N–C support. Alloying of Pt derived from H2PtCl6 with various iron-based species existing in forms of single-atom, metallic, and oxide states was confirmed by systematic characterization, and the Fe content in the support is important for PtFe alloy formation, and the corresponding electrochemical performance promotion has been identified. The as-synthesized best-performance PtFe/Meso-PDA-5 catalyst delivered a high potential of 0.925 V at a current density of 3 mA cm–2 and achieved a high mass activity of 497.5 mA mgPt–1 at 0.9 V for the ORR in 0.1 M HClO4. More importantly, only 17.9% mass activity loss was observed after 10k potential cycles of the accelerated deterioration test. The present work provides a strategy for facile synthesis of Pt-based alloy nanomaterials for ORR catalysis and highlights the importance of supports in alloy formation.