High-entropy spinel oxides (HE-SOs) with the first five transition metal elements were synthesized using a simple one-pot supercritical hydrothermal fluid processing method. Solid-solution cubic spinel oxide nanoparticles (average diameter = 18.6 nm) were successfully synthesized. The overpotential for the electrochemical oxygen evolution reaction (OER) on HE-SOs was 330 mV (at 10 mA cm–2 in 1 M KOH), and the value of the Tafel slope was 36.7 mV dec–1, demonstrating that the HE-SO functioned as an efficient OER catalyst. This work can provide a simple synthesis strategy for multimetal elements containing oxides for a variety of catalytic reactions and applications.