The hot deformation behavior of Ti–6Al–4V alloy with starting fully lamellar microstructure was investigated by conducting isothermal hot compression tests at the temperature of 700–1000 °C and strain rate of 0.001–10 s−1. The deformation activation energy is calculated to be 342 kJ/mol at temperatures from 750 to 850 °C, whereas the higher apparent activation energy of 610 kJ/mol is obtained at a high temperature regime of 900–1000 °C. The relationship between the dynamic softening behavior and deformation parameters was analyzed by power dissipation efficiency η, which shows an increasing trend as the deformation temperature increases and strain rate decreases, respectively. Processing maps were constructed. The instability flow is dominated by the presence of adiabatic shear bands, and the dynamic softening is mainly caused by a combination effect of dynamic recrystallization and dynamic recovery. Moreover, straining is found to have a positive effect on lowering the phase transformation temperature.