Bone is similar to fiber-reinforced composite materials made up of distinct phases such as osteons (fiber), interstitial bone (matrix), and cement lines (matrix-fiber interface). Microstructural features including osteons and cement lines are considered to play an important role in determining the crack growth behavior in cortical bone. The aim of this study is to elucidate possible mechanisms that affect crack penetration into osteons or deflection into cement lines using fracture mechanics-based finite element modeling. Cohesive finite element simulations were performed on two-dimensional models of a single osteon surrounded by a cement line interface and interstitial bone to determine whether the crack propagated into osteons or deflected into cement lines. The simulations investigated the effect of (i) crack orientation with respect to the loading, (ii) fracture toughness and strength of the cement line, (iii) crack length, and (iv) elastic modulus and fracture properties of the osteon with respect to the interstitial bone. The results of the finite element simulations showed that low cement line strength facilitated crack deflection irrespective of the fracture toughness of the cement line. However, low cement line fracture toughness did not guarantee crack deflection if the cement line had high strength. Long cracks required lower cement line strength and fracture toughness to be deflected into cement lines compared with short cracks. The orientation of the crack affected the crack growth trajectory. Changing the fracture properties of the osteon influenced the crack propagation path whereas varying the elastic modulus of the osteon had almost no effect on crack trajectory. The findings of this study present a computational mechanics approach for evaluating microscale fracture mechanisms in bone and provide additional insight into the role of bone microstructure in controlling the microcrack growth trajectory.