The work-hardening behavior of Cu–Ni alloys with high stacking-fault energies (SFEs) is experimentally investigated under uniaxial compression. It is found that, with the increase of Ni content (or short-range clustering, SRC), the flow stress of Cu–Ni alloys is significantly increased, which is mainly attributed to an enhanced contribution of work-hardening. An unexpected multistage (including Stages A, B, and C) work-hardening process was found in this alloy, and such a work-hardening behavior is essentially related to the existence of SRC structures in alloys. Specifically, during deformation in Stage B (within the strain range of 0.04–0.07), the forming tendency to planar-slip dislocation structures becomes enhanced with an increase of SRC content (namely, increase of Ni content), leading to the occurrence of work-hardening rate recovery in the Cu–20at.% Ni alloy. In short, increasing SRC in the Cu–Ni alloy can trigger an unexpected multistage work-hardening process, and thus improve its work-hardening capacity.