The dynamic mechanical behavior and microstructure evolution of titanium alloy Ti6Al4V under shock compression at temperatures ranging from 25 ℃ to 800 ℃ and strain rates from 2000 s⁻¹ to 7000 s⁻¹ were studied by using a split Hopkinson pressure bar. The temperature dependence and strain rate sensitivity of the material’s mechanical response were analyzed, and a modified Johnson-Cook model that could accurately characterize the plastic flow behavior of the material was developed. The results show that Ti6Al4V exhibited significant strain hardening, strain rate strengthening, strain rate plasticity, and temperature softening effects. With increasing loading temperature and strain rate, the material’s strain hardening effect is weakened. The temperature sensitivity is significantly decreased with increasing loading temperature. The strain rate sensitivity factor is negatively correlated with the loading temperature, and it shows a downward trend as the true strain increased. At high temperatures and high strain rates, fine equiaxial α phase, elongated α phase, and massive α phase replace the initial equiaxial α phase as the typical microstructure features of Ti6Al4V. The modified Johnson-Cook model that considers the effect of rate-temperature coupling and adiabatic temperature rise can accurately predict the plastic flow stress-strain response of Ti6Al4V.