Material flow and heat generation by tool shoulder during Friction Stir Welding (FSW) significantly alters the microstructural and thermomechanical behavior of joints. The effect of shoulder size on mechanical properties of joints has not yet been reported in the FSW of Tailor-Welded Blanks (TWBs). This article reports the effect of shoulder size on joint quality in FSW of TWBs between 6.35 mm thick plates of AA2024-T3 and 2.5 mm thick plates of AA7475-T7 alloys in butt joint configuration fabricated under shoulder sizes: 18 mm, 20 mm, and 22 mm. Microstructural evaluation of FSWed joints reveals a significant increase in grain size with shoulder size. The X-ray energy-dispersive spectroscopic (EDS) elemental maps reveal the presence of fine second phase particles in the stir zone. The progressive elimination of void defects with the increase in shoulder size was observed. The tensile testing reveals the highest strength of joints fabricated via shoulder size of 18 mm. Fractographic analyses of broken tensile specimens showed the mixed mode of failure in all the welded specimens.