An Ag–Ni semi-empirical potential was developed to simulate the segregation of Ni solutes at Ag grain boundaries (GBs). The potential combines a new Ag potential fitted to correctly reproduce the stable and unstable stacking fault energies in this metal and the existing Ni potential from Mendelev et al (2012 Phil. Mag. 92 4454–69). The Ag–Ni cross potential functions were fitted to ab initio data on the liquid structure of the Ag80Ni20 alloy to properly incorporate the Ag–Ni interaction at small atomic separations, and to the Ni segregation energies at different sites within a high-energy Σ9 (221) symmetric tilt GB. By deploying this potential with hybrid Monte Carlo/molecular dynamics simulations, it was found that heterogeneous segregation and clustering of Ni atoms at GBs and twin boundary defects occur at low Ni concentrations, 1 and 2 at%. This behavior is profoundly different from the homogeneous interfacial dispersion generally observed for the Cu segregation in Ag. A GB transformation to amorphous intergranular films was found to prevail at higher Ni concentrations (10 at%). The developed potential opens new opportunities for studying the selective segregation behavior of Ni solutes in interface-hardened Ag metals and its effect on plasticity.