The development of electron beam welding technology is advancing toward higher voltages, greater power, extended lifespan, improved stability, and intelligent control, positioning it as an ideal welding technique for thick titanium alloy structures. In this study, a high-voltage electron beam was employed to weld 20 mm thick TA15 titanium alloy, systematically analyzing the effects of 100 kV, 120 kV, and 150 kV accelerating voltages on the microstructure and mechanical properties of the weld joints under consistent heat input. Additionally, the thermal action mechanisms of accelerating voltages on the welding process were also investigated. The results show that accelerating voltage significantly impacts local undercooling within the weld joint, and as the accelerating voltage increases, the undercooling degree decreases, thereby promoting the diffusion and transformation of alloying elements in TA15 titanium alloy, resulting in the formation of fine needle-like α′ phase and a small amount of lamellar α phase. At 150 kV, the room-temperature ductility of the TA15 titanium alloy was notably improved due to the increased presence of the β-phase and high-angle grain boundaries in the weld, which in turn enhances the alloy’s plastic deformation capacity. These findings offer crucial theoretical insights for the engineering application of high-voltage, high-power electron beam welding in the fabrication of thick and tough titanium alloys.