The microstructure and dynamic material properties of Ti–6Al–2Zr–1Mo–1V (TA15) titanium alloy are very sensitive to process parameters, which directly determine the service properties. To explore and understand the deformation behavior and the optimization of the deformation process, a microstructure-evolution model is needed not only to phenomenologically describe the hot deformation process, but also to reflect the interaction between deformation and microstructure evolution and to reveal the deformation mechanism. In this article, we present an experimental investigation of the microstructure-evolution law and the softening mechanism of TA15 deformation in the two-phase region. By using the internal-state-variable method, a set of mechanically based equations that model the evolution of the dislocation density, the recrystallization and the grain size are developed for the TA15 alloy. By integrating the microstructure-evolution model into the DEFORM-3D software package, we predict microstructure evolution during an isothermal, compressive-deformation process, and the model is verified by comparing the experimental results with the calculation. Using the model a simulation and grain-size prediction of the TA15 large-component isothermal forming are carried out, and the results are confirmed experimentally.