• A universal synthetic strategy was proposed to construct heteroatom axially coordinated Fe–N4 single-atom seawater catalyst materials (Cl–Fe–N4 and S–Fe–N4).
• The Cl–Fe–N4 catalyst achieves a limiting current density of 5.8 mA cm−2 and a half-wave potential of 0.931 V vs. RHE in alkaline synthetic seawater, outperforming commercial Pt/C (40 wt%).
• The seawater-based zinc-air battery fabricated with Cl–Fe–N4 demonstrates a power density of 187.7 mW cm−2 at 245.1 mA cm−2 and maintains stable cycling performance for 200 h.
• Density functional theory calculations revealed that axial heteroatom coordination regulates the electron center of Fe single atoms, enhancing ORR activity and Cl− poisoning resistance.