In this paper, the crack initiation mechanism of dissimilar aluminum alloy welded joints was studied. The base metals are 2219 aluminum alloy and 5A06 aluminum alloy, the filler wires are 2325 and 5B06. The microstructure was analyzed by the optical microscope (OM), scanning electron micrograph (SEM) and energy dispersive spectroscopy (EDS). Results showed that the weld hardness obtained by the 2325 is about 100 HV and that by 5B06 is about 80 HV. Compared with heat affected zone (HAZ) of the weld obtained by 2219 and 2325, the grain growth of HAZ of the weld obtained by 5A06 and 2325 is not so obvious that the joint softening phenomenon doesn’t exist. The diffusion and segregation of Mg element and Cu element can be obviously observed in the welded fusion zone (FZ) obtained by 2325 and 5A06, and that by 5B06 and 2219. Compared with the welded joint obtained by 5B06 filler wire, the great cracking tendency can be found in dissimilar welded joint obtained by 2325 filler wire, because there is no obvious low melting eutectics in welded joint by 5B06 filler wire. Many low melting eutectics (Al2CuMg and CuAl2) present in the welded joint by 2325 filler wire, and the Al2CuMg eutectics are fundamental cause for the crack initiation.