The fatigue crack propagation behavior in the overaged Al-Zn-Mg-Cu alloy was characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy and electron backscatter diffraction. The results revealed that a fatigue crack tended to transgranularly propagate in the near-threshold regime, whereas intergranular crack propagation was dominant at the high ΔK regime. The transition of crack propagation from a transgranular to an intergranular path that occurred in the Paris regime was strongly influenced by the misorientation of adjacent grains and precipitate free zones. In addition, a crystallographic model of crack propagation was proposed to interpret the transition. The fatigue short crack propagation on a single slip plane was responsible for the formation of a transgranular propagation path in the near-threshold regime. The fatigue long crack propagation, which was conducted by a duplex slip mechanism in the Paris regime, led to the formation of fatigue striations. The formation of a zigzag crack in the near-threshold regime was ascribed to the high misorientation of adjacent grains.