Single‐atom catalysts (SACs) have attracted extensive interest to catalyze the oxygen reduction reaction (ORR) in fuel cells and metal–air batteries. However, the development of SACs with high selectivity and long‐term stability is a great challenge. In this work, carbon vacancy modified Fe–N–C SACs (Fe _H –N–C) are practically designed and synthesized through microenvironment modulation, achieving high‐efficient utilization of active sites and optimization of electronic structures. The Fe _H –N–C catalyst exhibits a half‐wave potential ( E _1/2 ) of 0.91 V and sufficient durability of 100 000 voltage cycles with 29 mV E _1/2 loss. Density functional theory (DFT) calculations confirm that the vacancies around metal–N ₄ sites can reduce the adsorption free energy of OH*, and hinder the dissolution of metal center, significantly enhancing the ORR kinetics and stability. Accordingly, Fe _H –N–C SACs presented a high‐power density and long‐term stability over 1200 h in rechargeable zinc–air batteries (ZABs). This work will not only guide for developing highly active and stable SACs through rational modulation of metal–N ₄ sites, but also provide an insight into the optimization of the electronic structure to boost electrocatalytical performances.