The face-centered-cubic (fcc) CoCrFeMnNi high-entropy alloy suffers from low strength and wear resistance at ambient temperature. Herein, we developed a strategy to overcome the strength/ductility trade-off and simultaneously increase the wear resistance via the in situ formation of uniformly dispersed MnO nanoparticles in an ultrafine-grained fcc FeMnNi matrix. The obtained equiatomic FeMnNi alloy exhibited a high yield strength of up to 912 MPa and an elongation of 19 pct. Grain boundary and oxide-dispersion-strengthened were found to be the main strengthening mechanisms. Ball-on-disk wear tests showed that the FeMnNi alloy had low wear rates in the order of 10-10 mm/(N m) upon sliding against an alumina ball, and the wear mechanism changed from abrasive wear to oxidation and fatigue wear at high loads and sliding velocities. The presence of MnO nanoparticles hindered the severe plastic flow of the fcc matrix during sliding. The excellent combination of strength, ductility, and tribological performance of the present alloy renders it as a promising candidate for structural applications.