Water oxidation catalysis plays a pivotal role in the context of the worldwide interest for sustainable energy. Finding cost-effective and robust catalysts to replace the state-of-the-art noble metal materials is hence urgent. In this work, we develop a molecular iridium complex that selectively and uniformly anchors on the surface of manganese oxide which is interconnected with a nitrogen-doped carbon forming a nanorod material. In the subsequent pyrolysis step, isolated Ir atoms are created on the manganese oxide surface and they strongly interact with the adjacent Mn. Through physicochemical characterization and computational studies, we demonstrate that the incorporation of Ir single-atom species in the MnOx/N–C composite promotes the electrochemical water oxidation catalysis. The new material shows excellent activity in the oxygen evolution reaction in 0.1 M KOH with an overpotential of 250 mV at 10 mA cm−2. Importantly, compared to a sample conventionally prepared with H2IrCl6, the novel Ir–MnOx/N–C catalyst not only is more efficient, but also demonstrates improved redox stability without suffering from Ir leaching. Our approach opens up new opportunities for the rational design of site-isolated materials for catalysis in the field of energy applications.