The microstructure and mechanical properties of 7075/6061 high-strength dissimilar aluminum alloy fusion welds, after TiC nanoparticle-assisted welding and heat treatment, were discussed, and their fatigue performance was analyzed. The results indicate that the significant increase in hardness at the weld zone with T6 treatment compared to T5 is due to the solution treatment providing supersaturated solid solution for subsequent aging precipitation. T5 treatment causes the precipitation in the heat affected zones, thereby increasing the hardness of these regions. The joints exhibit excellent yield strength and tensile strength after heat treatment, with the elongation performance being optimal in T6 state. The fatigue performance of dissimilar aluminum alloy joints treated with nanoparticle and heat treatment is superior to the joints with single riveting. Porosity defects and microcracks generated during welding are prone to stress concentration, with interconnected pores and easily propagating cracks forming fatigue sources for pores and cracks. The crack propagation behavior is influenced by the pinning effect of TiC nanoparticles at the grain boundaries, and the second phase particles hinder crack propagation along the grain boundaries, forcing cracks to extend towards the 6061 side or the HAZ of the lower strength 6061 matrix. It demonstrates that the method of combining nanoparticle-assisted melt inert-gas welding and T6 heat treatment improves the fatigue life of 7075/6061 dissimilar aluminum alloy joints.