In this study, ultrasonic shot peening (USP) was used to enhance the surface of a Ti-6Al-4V alloy. Samples treated with different amplitudes were characterized and their wear resistance was tested and analyzed. The results demonstrate that the surface morphology of the Ti-6Al-4V alloy changed significantly after USP treatment, and the surface roughness increases at first, then stabilizes as the amplitude increases. The surface grain of the material is refined due to severe plastic deformation, and the average grain size after USP treatment is 27.93% finer than the original sample. Due to the effect of fine grain strengthening and work hardening, the microhardness of the material's near-surface layer is also enhanced in varying degrees, showing a gradient decrease throughout the depth of the cross-section. Furthermore, USP produces compressive residual stress as high as −791.01 MPa in the near-surface layer. When the USP amplitude is 80% and the treatment time is 240 s, the wear resistance of Ti-6Al-4V alloy is substantially enhanced under the combined action of hardness, compressive residual stress, and surface pits, reducing wear resistance. The wear mechanism is primarily abrasive wear and oxidation wear.