The effect of friction stir welding (FSW) parameters on the microstructure and mechanical properties of 5.6 mm thick 2219Al-T6 joints was investigated in detail. While the sound FSW joints could be obtained under lower rotation rates of 400-800 rpm and welding speeds of 100-800 mm/min; higher rotation rates of 1200-1600 rpm easily led to the tunnel and void defects. The FSW thermal cycle resulted in low hardness zones (LHZs) on both retreating side (RS) and advancing side (AS). The LHZs may be located at the interface between the nugget zone (NZ) and the thermo-mechanically affected zone (TMAZ), at the TMAZ, or at the heat affected zone under the varied welding parameters. The tensile strength of FSW 2219Al-T6 joints increased when increasing the welding speed from 100 to 800 mm/min, and was weakly dependent on the rotation rates from 400 to 1200 rpm. The FSW 2219Al-T6 joints fractured along the LHZ on the RS.