Metal-air batteries face a great challenge in developing efficient and durable low-cost oxygen reduction reaction (ORR) electrocatalysts. Single-atom iron catalysts embedded into nitrogen doped carbon (Fe-N-C) have emerged as attractive materials for potential replacement of Pt in ORR, but their catalytic performance was limited by the symmetrical electronic structure distribution around the single-atom Fe site. Here, we report our findings in significantly enhancing the ORR performance of Fe-N-C by moderate Fe2O3 integration via the strong electronic interaction. Remarkably, the optimized catalyst (M−Fe2O3/FeSA@NC) exhibits excellent activity, durability and good tolerance to methanol, outperforming the benchmark Pt/C catalyst. When M−Fe2O3/FeSA@NC catalyst was used in a practical zinc-air battery assembly, peak power density of 155 mW cm−2 and specific capacity of 762 mA h gZn−1 were achieved and the battery assembly has shown superior cycling stability over a period of 200 h. More importantly, theoretical studies suggest that the introduction of Fe2O3 can evoke the crystal field alteration and electron redistribution on single Fe atoms, which can break the symmetric charge distribution of Fe-N4 and thereby optimize the corresponding adsorption energy of intermediates to promote the O2 reduction. This study provides a new pathway to promote the catalytic performance of single-atom catalysts.