The development of facile, efficient synthesis method to construct low‐cost and high‐performance single‐atom catalysts (SACs) for oxygen reduction reaction (ORR) is extremely important, yet still challenging. Herein, an atomically dispersed N, S co‐doped carbon with abundant vacancy defects (NSC‐vd) anchored Fe single atoms (SAs) is reported and a vacancy defects inductive effect is proposed for promoting electrocatalytic ORR. The optimized catalyst featured of stable Fe─N3S1 active sites exhibits excellent ORR activity with high turnover frequency and mass activity. In situ Raman, attenuated total reflectance surface enhanced infrared absorption spectroscopy reveal the Fe─N3S1 active sites exhibit different kinetic mechanisms in acidic and alkaline solutions. Operando X‐ray absorption spectra reveal the ORR activity of Fe SAs/NSC‐vd catalyst in different electrolyte is closely related to the coordination structure. Theoretical calculation reveals the upshifted d band center of Fe─N3S1 active sites facilitates the adsorption of O2 and accelerates the kinetics process of *OH reduction. The abundant vacancy defects around the Fe─N3S1 active sites balance the OOH* formation and *OH reduction, thus synergetically promoting the electrocatalytic ORR process.