The purpose of this study was to investigate whether bone fracture properties change with species (humans, baboon, canine, bovine, and rabbit). A single-layer compact sandwich (SCS) specimen and fractography were employed to evaluate bone fracture properties. In conjunction with measurements of the density and volume fractions of the mineral and organic phases, bone microstructure were also investigated. The results of this study indicate that bone fracture properties vary considerably with species. These differences are most likely due to variations in microstructural and compositional properties of bone (mineral and collagen) between the species. Baboon bone exhibited most similar fracture, microstructural, and compositional properties compared to humans. However, significant differences were found in bone fracture properties between humans and the other three animal species. These differences were reflected either in bone microstructures or compositional properties. This interspecies comparison facilitates a better understanding of animal models and suitable use of the animal models in future bone fracture studies.