Abstract: Hot deformation of sintered billets by powder metallurgy (PM) is an effective preparation technique for titanium alloys, which is more significant for high-alloying alloys. In this study, Ti–6.5Al–2Zr–Mo–V (TA15) titanium alloy plates were prepared by cold pressing sintering combined with high-temperature hot rolling. The microstructure and mechanical properties under different process parameters were investigated. Optical microscope, electron backscatter diffraction, and others were applied to characterize the microstructure evolution and mechanical properties strengthening mechanism. The results showed that the chemical compositions were uniformly diffused without segregation during sintering, and the closing of the matrix craters was accelerated by increasing the sintering temperature. The block was hot rolled at 1200°C with an 80% reduction under only two passes without annealing. The strength and elongation of the plate at 20–25°C after solution and aging were 1247 MPa and 14.0%, respectively, which were increased by 24.5% and 40.0%, respectively, compared with the as-sintered alloy at 1300°C. The microstructure was significantly refined by continuous dynamic recrystallization, which was completed by the rotation and dislocation absorption of the substructure surrounded by low-angle grain boundaries. After hot rolling combined with heat treatment, the strength and plasticity of PM-TA15 were significantly improved, which resulted from the dense, uniform, and fine recrystallization structure and the synergistic effect of multiple slip systems.