Seawater electrolysis represents a viable alternative for large-scale synthesis of hydrogen (H2), which is recognized as the most promising clean energy source, without relying on scarce fresh water. However, high energy cost and harmful chlorine chemistry in seawater limited its development. Herein, an effective catalyst based on a ruthenium nanoparticle–Ti3C2 MXene composite loaded on nickel foam (RuO2–Ti3C2/NF) with an open, fine, and homogeneous nanostructure was devised and synthesized by electrodeposition for high performance and stable overall seawater splitting. To drive a current density of 100 mA cm–2, the RuO2–Ti3C2/NF electrode required a small overpotential of 85 and 351 mV for HER and OER in 1 M KOH with only a slight increase in 1 M KOH seawater (156 and 378 mV for, respectively, HER and OER). An assembled RuO2–Ti3C2/NF-based two-electrode cell required an overpotential of only 1.84 V to acquire 100 mA cm–2 in 1 M KOH seawater and maintained its activity for over 25 h. This low cell voltage effectively prevented chlorine electrochemical evolution without anode protection. These promising results open up new avenues for the effective conversion of abundant seawater resources to hydrogen fuel.