This paper investigates the relationship between weld quality, influencing factors, microstructure and mechanical properties of laser spiral dissimilarity welding of 6082 high-strength aluminum alloy and DP980 high-strength dual-phase steel, focusing on the fatigue properties and fracture mechanism of 6082-DP980 dissimilar metal welded joints. The research shows that intermetallic compound layers (IMCs) dominate the fatigue crack initiation stage and part of the crack extension stage, two fatigue crack initiation modes are obtained, one is the main crack initiation mode along the FeAl and FeAl2 interlayer, and the other is the secondary crack initiation mode along the Fe3Al and FeAl interlayer. In the crack propagation stage, due to the diffusion of Fe and Al elements generated by IMCs during the welding process, solid solution strengthening, intergranular strengthening and grain boundary strengthening, in the fatigue crack propagation stage formed a hardened zone, hindering the main crack to continue to expand along the IMCs, the main crack shifted to the expansion of the 6082 base material, thus extending the fatigue life.