Double-sided friction stir welding (DS-FSW) demands a low requirement of the welding tool and equipment and can lower the heat input, showing advantages in joining thick-plate joints. However, the intrinsic twice thermal cycle inevitably leads to the twice grain growth and softening, troubling the performance of the joints. To alleviate this phenomenon, this work proposed an asymmetric DS-FSW (Asy-DS-FSW) in which the first weld and second weld are obtained via a large tool and a small tool, respectively. The results suggest that the Asy-DS-FSW effectively refines the grains and inhibits twice-grain growth in the 27 mm thick AA7A65 joints. The hardness of Asy-DS-FSW is higher and more homogeneously distributed than the conventional symmetric DS-FSW (Sym-DS-FSW). The ultimate tensile strength of the slices is enhanced by 0.5-11%, and the eased strain localization can be achieved by the Asy-DS-FSW, compared with the Sym-DS-FSW. This work offers valuable references to the high-quality joining of thick-plate aluminum alloys in aerospace.