AbstractSingle-atom catalysts (SACs) have attracted tremendous research interests in various energy-related fields because of their high activity, selectivity and 100% atom utilization. However, it is still a challenge to enhance the intrinsic and specific activity of SACs. Herein, we present an approach to fabricate a high surface distribution density of iridium (Ir) SAC on nickel-iron sulfide nanosheet arrays substrate (Ir₁/NFS), which delivers a high water oxidation activity. The Ir₁/NFS catalyst offers a low overpotential of ~170 mV at a current density of 10 mA cm⁻² and a high turnover frequency of 9.85 s⁻¹ at an overpotential of 300 mV in 1.0 M KOH solution. At the same time, the Ir₁/NFS catalyst exhibits a high stability performance, reaching a lifespan up to 350 hours at a current density of 100 mA cm⁻². First-principles calculations reveal that the electronic structures of Ir atoms are significantly regulated by the sulfide substrate, endowing an energetically favorable reaction pathway. This work represents a promising strategy to fabricate high surface distribution density single-atom catalysts with high activity and durability for electrochemical water splitting.