The oxygen evolution reaction (OER) is crucial for producing sustainable energy carriers. Herein, Ir (5 mol.%) doped inverse-spinel NiFe2O4 (Ir-NFO) nanoparticles deposited on Ni foam (NF) by scalable solution casting are considered a promising OER electrocatalyst for industrial deployments. The Ir-NFO/NF (with minimal lattice distortion by uniform Ir doping) provides an OER overpotential of 251 mV (intrinsically outperforming NFO/NF and benchmarking IrO2/NF) and extraordinary robustness over 130 days at 100 mA cm−2. In situ X-ray absorption spectroscopy reveals oxidation only for Fe on NFO, whereas concurrent generation of higher-valent Ni and Fe occurs on Ir-NFO during OER. Density functional theory calculations further demonstrate that Ir substitutes the sublayer Ni octahedral site and switches the main active reaction center from FeOhFeTd bridge site (FeOFe) on NFO to NiOh–FeTd bridge site (NiOFe active motif) on Ir-NFO for a co-catalytic OER. This study sheds new light on precious-metal doped Ni-Fe oxides, which may be applicable to other binary/ternary oxide electrocatalysts.​