Abstract: Based on the method of ABAQUS and FRANC 3D co-simulation, the crack growth analysis and life prediction were carried out on the compact tensile specimens with precracks in different zones of 2024-T4 aluminum alloy friction stir welding (FSW) joints, and the causes of the differences in crack propagation behavior in different zones were analyzed. The results showed that the crack tip stress intensity factor increased with the growth in crack length, and the crack forward expansion path basically expanded along the straight line. ABAQUS and FRANC 3D joint simulation method analysis of different areas of crack tip stress intensity factor and crack propagation path basically consistent with the theoretical calculation and test results, verifying that the model accuracy of the joint simulation by subregion is satisfactory. The relative errors of the life prediction results in different zones and the test results are about 5%, so it is accurate and feasible to predict the life of the joint by regional co-simulation. The fatigue striation spacing at the crack propagation fracture in different zones is different, resulting in the fatigue life of the prefabricated crack in three zones from low to high: the heat affected zone, perpendicular to the weld direction, and the weld core zone.