The development of atomically dispersed multi-metallic catalysts is imperative for tailoring catalytic performance and elucidating structure–activity relationships. However, synthesizing such precisely engineered architectures while maintaining atomic dispersion of distinct metal centers remains a formidable challenge due to thermodynamic instability and synthetic complexity. We herein propose a topological confinement pre-anchoring strategy via pre-anchoring spatially resolved Zn/Fe dual-metal sources in a structurally engineered metal–organic framework precursor to synthesize atomically dispersed ZnFe bimetallic single-atom catalysts. Extended X-ray absorption fine structure measurements and X-ray absorption near-edge structure reveal that the atomically dispersed Zn/Fe metal sites and electronic redistribution in ZnFe bimetallic single-atom catalysts. The ultrahigh surface area, hierarchical pore, and synergistic effect between Zn/Fe can greatly favor the exposure of the active site, mass transport, and improvement of intrinsic activity. Consequently, the ZnFe bimetallic single-atom catalyst demonstrates superior oxygen reduction reaction performance, achieving a half-wave potential of 0.86 V and delivering a kinetic current density of 10.1 mA cm⁻² at 0.85 V versus RHE in 0.1 M KOH electrolyte. These metrics not only surpass those of commercial Pt/C, but also rival the highest-performing catalysts reported to date. The Zn-air battery built with ZnFe bimetallic single-atom catalyst exhibits high power density (278.5 mW cm⁻²) and specific discharging capacities (657 mAh g⁻¹). This work provides a new design pathway for constructing atomically dispersed multi-metal electrocatalysts for high-performance energy-related applications.