Abstract Fission product accumulation and gas bubble microstructure evolution in nuclear fuels strongly influence their thermo-mechanical properties such as thermal conductivity, gas release, volume swelling and cracking, and hence fuel performance. In this paper, a general phase-field model is developed to predict gas bubble formation and evolution. Important materials processes and thermodynamic properties including the generation of gas atoms and vacancies, sinks for vacancies and gas atoms, elastic interaction among defects, gas re-solution, and inhomogeneity of elasticity and diffusivity are accounted for in the model. The results demonstrate the potential applications of the phase-field method in investigating: 1) heterogeneous nucleation of gas bubbles at defects; 2) effect of elastic interaction, inhomogeneity of material properties, and gas re-solution on gas bubble microstructures; and 3) effective properties from the output of phase-field simulations such as distribution of defects, gas bubbles, and stress fields.