Recent experiments show a binary Ni–V face-centred cubic (FCC) solid solution alloy possessing superior strength and work hardenability exceeding extant multiprincipal element alloys with a FCC solid solution structure. The outstanding mechanical properties can be attributed to V solid solution strengthening, but the mechanistic effects of V solutes and short-range order (SRO) on deformation behaviour remain unclear and perplexing. Here, we develop an extended modified embedded-atom method (XMEAM) interatomic potential for the binary Ni–V system to enable direct and accurate modelling of SRO and V–lattice defect interactions. The potential is fit to a broad range of lattice and defect properties from extant experiments and new density functional theory (DFT) calculations in multiple solid solution and intermetallic structures. Extensive benchmarks with molecular dynamics and Monte Carlo simulations show great accuracy and transferability of the developed potential in Ni–V solid solution alloys across a wide range of V concentrations as well as in intermetallic structures. In particular, the potential reproduces SRO, phase transitions, solute misfit volume and solute interaction with dislocations consistent with extant experiments and the Ni-rich side of the binary phase diagram. The new potential is also computationally efficient; its availability thus opens the essential path for large-scale, mechanistic modelling of plastic deformation and SRO effects in the Ni–V binary system with high fidelity and forms the foundation for developing other binary systems and extending to ternary systems.