<p>Electrocatalytic two-electron oxygen reduction reaction (2e⁻ ORR) in seawater offers a sustainable route for hydrogen peroxide (H₂O₂) production. However, due to the high concentration of Cl⁻ ions and competitive 4e⁻ ORR, there is a lack of efficient and long-term stable seawater electrocatalysts. Here we report a high-performance electrocatalyst design based on NiPS₃ nanosheets enabling efficient H₂O₂ production from seawater. Specifically, the NiPS₃ nanosheets deliver a 2e⁻ ORR selectivity of ∼98%, a H₂O₂ yield of 6.0 mol g_cat⁻¹ h⁻¹ and robust stability for over 1,000 h in simulated seawater. Underlying the exciting performance is the synergy of the S²⁻, Ni²⁺ and P⁴⁺ sites where the octahedral S²⁻ skeleton repels Cl⁻ ions, the Ni²⁺ sites enable the modest binding strength of *OOH intermediate, and the P⁴⁺ sites interact with H₂O to trigger the protonation of proximal O atom of *OOH. The seawater electrocatalysis system also allows for scalable synthesis of solid H₂O₂, tandem oxidation reaction of biomass to organic acid and direct use of the produced H₂O₂ as a sterilizing agent. Once integrated with photovoltaics, the solar-powered electrolysis device can operate in real seawater. Our findings pave the way for sustainable conversion of seawater into value-added products.</p>