TC4 titanium alloy is a key material for fabricating load-bearing frame beams in aircraft structures. Narrow gap laser welding offers considerable technical advantages and feasibility for joining thick TC4 titanium alloy plates. However, challenges remain because of substantial variations in the mechanical properties because different regions of the filler layer experience different thermal cycles and heat accumulations. These differences can lead to weak or defective layers, thereby compromising the overall mechanical performance of the weld. Ultrasonic vibration-assisted welding is an effective solution for improving the quality of narrow gap laser welding in thick-walled structures. This study combines the numerical simulations of the temperature and flow fields to investigate the mechanisms of microstructural regulation in different regions of the welded joint, focusing on the effect of ultrasonic vibration on mechanical properties across these areas. The results show that ultrasonic vibration produces a more uniform temperature distribution and increases the fluid flow velocity in the molten pool. Cavitation stress fields and the formation of numerous cavitation bubbles at grain boundaries in the shear direction facilitate grain refinement and promote a more homogeneous grain structure in the weld seam. In addition, the number of needle-like αʹ-martensite structures in the weld zone considerably increases. However, the grain refinement effect gradually weakens from the weld zone to the heat-affected zone. The application of ultrasonic energy improves the microhardness and impact toughness of the filler material layers. Notably, the improvement in the overall mechanical properties of the welded joint gradually declines as the depth from the weld seam increases.