The physically-based internal state variable (ISV) models were used to describe the changes of dislocation density, grain size, and flow stress in the high temperature deformation of titanium alloys in this study. The constants of the present models could be identified based on experimental results, which were conducted at deformation temperatures ranging from 1093 K to 1303 K, height reductions ranging from 20% to 60%, and the strain rates of 0.001, 0.01, 0.1, 1.0, and 10.0 s^-1. The physically-based internal state variable models were implemented into the commercial finite element (FE) code. Then, a three-dimensional (3D) FE simulation system coupling of deformation, heat transfer, and microstructure evolution was developed for the blade forging of Ti-6Al-4V alloy. FE analysis was carried out to simulate the microstructure evolution in the blade forging of Ti-6Al-4V alloy. Finally, the blade forging tests of Ti-6Al-4V alloy were performed to validate the results of FE simulation. According to the tensile tests, it is seen that the mechanical properties, such as tensile strength and elongation, satisfy the application requirements well. The maximum and minimum differences between the calculated and experimental grain size of primary α phase are 11.71% and 4.23%, respectively. Thus, the industrial trials show a good agreement with FE simulation of blade forging.