To enhance the aerodynamic performance of Ti6Al4V functional components, this paper systematically investigated the femtosecond laser processing technology for surface drag-reduction microstructures, aiming to fabricate high-performance microstructures. (1) V-shaped, U-shaped, and rectangular micro-grooves were designed based on the boundary layer theory, and their drag-reduction mechanisms were elucidated through CFD numerical simulations. The results indicate that the V-shaped groove achieves a peak drag-reduction rate of 13.1% at a dimensionless depth of h⁺ = 15 and an aspect ratio of 1, primarily due to the formation of a low-velocity zone and the suppression of turbulent bursts by secondary vortices. (2) Through single-factor experiments, the influence laws of femtosecond laser process parameters on the V-shaped groove were explored. (3) Regression prediction models for groove dimensions were established using the Response Surface Methodology (RSM) to optimize the processing parameters. Under the optimized conditions, high-quality V-shaped groove arrays with a width of 55.9 μm and a depth of 55.5 μm were successfully fabricated on the Ti6Al4V surface, characterized by high consistency and a minimal heat-affected zone. This research provides an effective technical solution for the precision manufacturing of high-performance drag-reduction structures on titanium alloy surfaces.