A comprehensive coupled thermo-chemo-mechanical modeling framework is proposed in this work to study the reaction-diffusion phenomena taking place inside photovoltaics (PV). When exposed to hygrothermal conditions, the encapsulant ethylene-co-vinyl acetate (EVA) layers undergo chemical degradation that significantly influences the overall PV performance. Aiming at efficient thermo-mechanical modeling, the coupled displacement-temperature governing equations for the EVA layers are formulated, and its 3D finite element (FE) implementation is derived in detail. Subsequently, the chemical reaction-diffusion processes occurring in the EVA layers are described, and the corresponding numerical implementation is formulated with the consideration of spatial and temporal variation of diffusivity and chemical kinetic rates. Specifically, the thermo-mechanical solution accounting for the heat generation from chemical reactions is projected to the FE model of the reaction-diffusion system in order to determine the kinetic rates and diffusion coefficients for its subsequent analysis. The proposed modeling method is applied to simulate the evolution of reaction-diffusion species at different damp heat tests, and predictions show a very satisfactory agreement with the analytical solution and experimental electroluminescence images taken from the literature. Its capabilities to predict the spatio-temporal variation are demonstrated through the simulation of the humidity freeze test, where the cyclic temperature boundary condition is imposed. With this modeling framework, it is possible to evaluate the degradation of PV modules under varying environmental boundary conditions, thus providing a guideline to design new products tailored for specific climatic zones.