The multiscale model was established to predict the crack propagation behavior of γ-titanium aluminide (TiAl) alloys. The constitutive parameters of the cohesive zone model (CZM) of true twin (TT) γ/γ interface were obtained by molecular dynamics (MD). The mesoscopic model of polycrystalline γ-TiAl was generated via Voronoi method, and the CZM constitutive parameters were coupled into the model. The corresponding critical stress fracture diagrams with non-defect, blunt crack and blunt crack+central cavity defect were obtained. Furthermore, the polycrystalline model and the overall force-displacement curve were averaged by the geometric similarity, and the damage mechanism of γ-TiAl alloy was analyzed. At the same time, the macroscopic finite element model (FEM) was constructed according to the homogeneous material hypothesis. A cohesive region was built in the interested crack area, and then the force-displacement relationship and fracture toughness of γ-TiAl alloy was obtained through the FEM simulation of the compact tensile specimen. Finally, the results show that the comparison between the crack propagation behavior obtained from the macroscale finite element simulation and the experimental results proves the validity of the multiscale model. The defects have a significant sensitivity on the strength of the entire near-γ structure when the ratio of grain is the same, and meanwhile this analysis method can effectively connect various scales and predict the growth of cracks.