Tribology behaviors of energetic crystals play critical roles in the friction-induced hotspot in high-energy explosive, however, the binder and energetic crystals are not distinguished properly in previous investigations. In this study, for the first time, the nanoscale friction of β-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (β-HMX) crystal is studied with nanoscratch tests under the ramping load mode. The results show that the nanoscale friction and wear of β-HMX crystal, as a typical energetic material, is highly depended on the applied load. The friction coefficient of β-HMX crystal is initially high when no discernible wear is observed, and then it decreases to a stable value which varies from ~0.2 to ~0.7, depending on the applied load, scratch direction, and crystal planes. The β-HMX (011) surfaces show weakly friction and wear anisotropy behavior; in contrast, the β-HMX (110) surfaces show strongly friction and wear anisotropy behavior where the friction coefficient, critical load for the elastic–plastic deformation transition and plastic–cracking deformation transition, and deformation index at higher normal load are highly depended on the scratch directions. Further analyses indicate the slip system and direction of β-HMX surfaces play key roles in determining the nanoscale friction and wear of β-HMX surfaces. The obtained results can provide deeper insight into the friction and wear of energetic crystal materials.