The deformation mechanisms and dynamic softening behavior of a Ti–6Al–4V alloy with thick lamellar microstructures are studied by uniaxial hot tensile tests. The true stress first rapidly reaches a peak value because of the rapid dislocations proliferation and tangle, and then gradually decreases due to the dynamic softening with raising the deformation amount. The dynamic softening behavior is mainly induced by the severe dynamic globularization of lamellar α phases. The globularization of α phase is always accompanied by the formation of high‐angle grain boundaries (HAGBs). The fraction of globularized α phases increases with the increasing deformation temperature. The fracture mechanism is microvoid coalescence, i.e., in the initial stage of tensile deformation, the microvoids begin to emerge. With the increasing deformation amount, the number of microvoids increases, and the microvoids accumulate and accelerate to propagate until the final fracture. According to the experimental flow stress curves, a modified Arrhenius‐type equation and a Hensel–Spittel (HS) model are developed to forecast the flow stresses. The average absolute relative error of the established strain‐compensated Arrhenius‐type (SCAT) and HS models are 6.108% and 3.385%, respectively. Both models can be well used to describe the hot tensile flow characteristics of the Ti–6Al–4V alloy with thick lamellar microstructures.