Abstract Transition metal sulfides with a multi‐elemental nature represent a class of promising catalysts for oxygen evolution reaction (OER) owing to their good catalytic activity. However, their synthesis remains a challenge due to the thermodynamic immiscibility of the constituent multimetallic elements in a sulfide structure. Herein, for the first time the synthesis of high‐entropy metal sulfide (HEMS, i.e., (CrMnFeCoNi)S x ) solid solution nanoparticles is reported. Computational and X‐ray photoelectron spectroscopy analysis suggest that the (CrMnFeCoNi)S x exhibits a synergistic effect among metal atoms that leads to desired electronic states to enhance OER activity. The (CrMnFeCoNi)S x nanoparticles show one of the best activities (low overpotential 295 mV at 100 mA cm −2 in 1 m KOH solution) and good durability (only slight polarization after 10 h by chronopotentiometry) compared with their unary, binary, ternary, and quaternary sulfide counterparts. This work opens up a new synthesis paradigm for high‐entropy compound nanoparticles for highly efficient electrocatalysis applications.