Taking into consideration the large positive mixing enthalpy of Cu–Mo, in this work, the relative content of Cu and Mo elements was adjusted to investigate the solidification process and microstructure formation of CrCu
x
FeMo
y
Ni high-entropy alloys. For CrCu0.5FeMoyNi (y = 0.5, 1) high-entropy alloys, many Cu-rich spheres were observed in the as-solidified microstructures, while macroscopic phase separation structures were obtained in CrCuFeMo
y
Ni (y = 0.5, 1) alloys. Liquid-phase separation occurred in high-entropy alloys when the enthalpy of mixing (ΔHmix)was positive, the valence electron concentration (VEC) was in a range of 8.09–8.44 and the difference in atomic radii (δ) was between 3.39 and 4.25. For lower positive ΔHmix, Cu-rich spheres were observed, while for higher positive ΔHmix, macroscopic phase-separated structures were obtained.