In the present study, 8 mm-thick 5251 aluminum alloy was self-reacting friction stir welded (SRFSW) employing an optimized friction stir tool to analyze the effect of welding speed from 150 to 450 mm/min on the microstructure and mechanical properties at a constant rotation speed of 400 rpm. The results indicated that high-quality surface finish and defect-free joints were successfully obtained under suitable process parameters. The microhardness distribution profiles on the transverse section of joint exhibited a typical “W” pattern. The lowest hardness values located at the heat-affected zone (HAZ) and the width of the softened region decreased with increasing welding speed. The tensile strength significantly decreased due to the void defect, which showed mixed fracture characteristics induced by the decreasing welding speed. The average tensile strength and elongation achieved by the SRFSW process were 242.61 MPa and 8.3% with optimal welding conditions, and the fracture surface exhibited a typical toughness fracture mode.