Precipitation-hardening high-entropy alloys (PH-HEAs) with good strength−ductility balances are a promising candidate for advanced structural applications. However, current HEAs emphasize near-equiatomic initial compositions, which limit the increase of intermetallic precipitates that are closely related to the alloy strength. Here we present a strategy to design ultrastrong HEAs with high-content nanoprecipitates by phase separation, which can generate a near-equiatomic matrix in situ while forming strengthening phases, producing a PH-HEA regardless of the initial atomic ratio. Accordingly, we develop a non-equiatomic alloy that utilizes spinodal decomposition to create a low-misfit coherent nanostructure combining a near-equiatomic disordered face-centered-cubic (FCC) matrix with high-content ductile Ni3Al-type ordered nanoprecipitates. We find that this spinodal order–disorder nanostructure contributes to a strength increase of ~1.5 GPa (>560%) relative to the HEA without precipitation, achieving one of the highest tensile strength (1.9 GPa) among all bulk HEAs reported previously while retaining good ductility (>9%).