The hot rolled and cold rolled-annealed plates of Al-Mg-Sc alloys were welded by friction stir welding. The hardness distribution and the tensile properties of welded joints were measured; the relationships between the microstructure and the properties of the welded joints were studied by means of optical microscopy and transmission electron microscopy. The results show that the welding coefficients of two plates are as high as 92%, the hardness and strength of their weld nugget zones are the lowest, and the fracture of their welded joints happens at weld nugget zones during tensile testing. The decrease of the substructure strengthening caused by the partial recrystallization and the loss of precipitation strengthening from Al3(Sc,Zr) particles result in the decline of hardness and strength of Al-Mg-Sc alloy welded joints.