Cortical bone is a transversely isotropic material, and the mechanical properties may be related to the loading direction on the osteon. Therefore, analyzing the differences in the failure processes of cortical bone under different loading conditions is necessary to explore the measures for reducing the incidence of fracture. In this study, to investigate the effects of different loading directions on the fracture performance in the cortical bone, a numerical method that could simultaneously simulate the failure processes in the cortical bone structure under compression and bending loads was established based on continuum damage mechanics theory. The prediction accuracy and feasibility of the numerical method were first verified by comparing with the corresponding experimental results. Then, the differences in the failure process and fracture performance of the same cortical bone structure under compression and bending loads were investigated. The simulation results indicated that for the same structure, the slip-open failure mode appeared under compression load, and the crack propagated along a certain angle to the loading direction;​ the tension-open failure mode appeared under bending load, and the crack propagated along the direction perpendicular to the loading direction. Meanwhile, the fracture load was greater and the fracture time was later in the compression than in the bending condition. These phenomena stated that discrepant failure processes and fracture patterns occurred in the same cortical bone structure under different loading conditions. The main reason may be related to the tension–compression asymmetry and transversely isotropic characteristics in the cortical bone material. The fracture simulations in the cortical bone under different loading conditions could improve the prediction accuracy in bone biomechanics and provide the prevention method for cortical bone damage and fracture.