Although great progresses in the fracture mechanisms and deformation behaviors of cortical bones have been achieved, the effective methods to predict the surface fracture path of cortical bones are still difficult. By using depth-sensing nanoindentation measurement technique, the hardness distribution map of cortical bones was obtained through nanoindentation array. Combined with the compressive tests under approximate in vivo environment and micro computed tomography (CT) analysis, the correlation between hardness distribution map and compressive fracture path on the cross section of cortical bone was established. Through extracting the high hardness regions from the hardness distribution map and connecting the high hardness regions combined with the minimum directional derivative principle, the fracture path on cross section under compressive stress was accurately predicted. The feasibility of the prediction method was verified through the comparison between the fitted and actual fracture paths of specimens with sampling orientations of 90° and 45°. The relation between the regions where the fracture propagation path passed through and distribution of Haversian canals were also analyzed.