Recent experimental and theoretical findings suggest that nanocrystalline binary alloys can be stabilized against interface-driven homogenization processes via grain boundary (GB) solute segregation mechanism. However, a detailed understanding of this process requires detangling the thermodynamic aspect, GB energy, from the kinetic one, GB mobility. In this work, we present a diffuse-interface model of GB segregation in binary metallic alloys that is capable of accounting for bulk thermodynamics, interfacial energies, and the interaction of alloying elements with GBs. In addition, the model presented herein extends current treatments by independently treating solute–solute interactions within both the bulk grain and GB regions, allowing for deviations from dilute and ideal systems and the ability to account for phase separation processes occurring in conjunction with grain growth. Starting with the analytical treatment of one-dimensional (1D) systems, we investigate the dependence of the GB energy, and subsequently the driving force for grain growth, on the segregation model parameters. More specifically, classic GB segregation isotherms are recovered in the limit of 1D infinite grains. Simulation results of two-dimensional systems reveal regimes of increased thermal stability, and highlight the importance of the thermodynamic model parameters of both bulk grain and GBs on grain growth processes. In broader terms, our modeling approach provides further avenues to explore GB solute segregation and its role in stabilizing polycrystalline aggregates.