Minimizing the use of iridium (Ir) in proton exchange membrane water electrolyzers (PEMWEs) is essential for hydrogen production without carbon emission. Herein, layered monoclinic iridium nickel oxide (IrNiOx) platelets were synthesized using the molten salt method and used for the oxygen evolution reaction (OER) in a PEMWE. The IrNiOx hexagonal platelets consist of the edge-sharing octahedral framework, in which Ni atoms replace Ir sites in the crystalline lattice. Thin IrNiOx platelets exhibited high OER activity with suppressed Ni dissolution from the bulk lattice in acidic media. When the platelets were applied in a membrane electrode assembly (MEA), they presented improved interconnectivity in the catalyst layer, facilitating electron transfer. Even at a low Ir loading of 0.2 mgIr cm–2, the platelets presented good performance with an initial cell voltage of 1.70 V at a current density of 1 A cm–2. Despite the use of a Ti porous transport layer (PTL) without Pt coating, the PEMWE operated stably for 150 h, exceeding the performance achievable by commercial Ir oxide and rutile IrO2. When a Pt-coated Ti PTL was used, the PEMWE could be operated stably for 500 h. Incorporating earth-abundant transition metals into the Ir oxide lattice can be an effective way to minimize the use of Ir in PEMWEs.