According to the actual size parameters, the finite element model (FEM) of friction stir welding (FSW) was established, and the FEM was updated by experiments. The FSW of the 2A14- T6 high-strength aluminum alloy was simulated under a reasonable welding process parameter range, and the welding process parameters with good simulation effect were determined. The test was carried out under the same parameters, and the axial force of the FSW tool and temperature of the workpiece measuring point were collected. The comparison between the simulated data and the experimental data is reasonable, indicating the correctness of the FEM. The microstructure analysis of the welded joint shows that the grain size in the upper part of the weld nugget was smaller than that in the middle and lower parts, and there are obvious boundaries of grain size in each region of the joint. The hardness of the joint in the upper layer is higher than that in the middle and lower layers, and the minimum Vickers hardness value of the joint appears near the interface between the thermo-mechanically affected zone and the heat-affected zone on both sides of the weld. Tensile testing shows that the strength coefficient of the joint reaches 82.5% under this process parameter, and the sample breaks at the intersection of the material flow during stretching. After analyzing the final mechanical properties of the joint, we found that a degree of aerospace application can be achieved. Under this parameter, the welding test was carried out on the top cover of the rocket fuel tank. Firstly, melon valve welding, which is relatively difficult in welding conditions, was carried out, and a high-quality joint with good surface and no defects was obtained.