This work involves studying the effects of applying various designed hot-rolling strategies, using the uniaxial hot compression regimes of the Gleeble 3500 thermo-mechanical simulator on the microstructure, flow behavior, and productivity of Ti-6Al-4V alloy. These strategies were then practically implemented using a rolling mill to produce finished sheets with a thickness of 3 mm. The tensile properties of these finished Ti-6Al-4V sheets were examined, aiming at attaining the optimum rolling strategy conditions that result in upgrading the mechanical performance of the alloy. The undertaken hot-rolling strategies can be divided into two main groups; both comprise applying a total amount of deformation of 75% at a constant strain rate of 0.1 s−1. The first group, isothermal hot rolling regime (IR), includes three strategies and involves applying the total amount of deformation at constant temperatures, i.e., 900, 800, and 750 °C. The second group, non-isothermal hot rolling regime (NIR), includes three strategies and involves partitioning the total amount of deformation into multi-step deformation at variable temperatures in a range of 900–750 °C. The dynamic flow softening is dominant in all IR strategies after the flow stress attains the peak at a low strain value. Then, dynamic flow softening occurs due to the dynamic recrystallization and α phase spheroidization, while a combination of flow softening and hardening takes place on the different passes of the NIR strategies. The designed hot-rolling strategies result in finished sheets with a fine multimodal microstructure that fructifies different mechanical properties that can be employed for different industrial purposes.