Knowledge of the intrinsic properties of hydroxyapatite (HAp) single crystals is important for the design of natural systems and will assist further improvements of manufactured biomaterials. Nanoindentation provides a useful tool for determining mechanical properties such as the hardness, elastic modulus and fracture toughness of small samples. A Berkovich indenter was placed on the side and basal planes of a natural single crystal of Durango HAp. The hardness and elastic modulus values obtained revealed higher values for the base (7.1 and 150.4 GPa) compared to the side (6.4 and 143.6 GPa). The cracking threshold, i.e., the load at which cracking initiates, revealed earlier crack formation on the base (at 8 mN) compared to the side (at 11 mN). Fracture toughness was measured as 0.45 ± 0.09 and 0.35 ± 0.06 MPa m1/2 for the side and basal plane, respectively. These results suggest that crystals are less prone to cracking and resist microcrack events better on the side, which is useful in bone, while exposing the base, the hardest face, to minimize mass loss from abrasion with teeth.