In ultra-precision machining, material anisotropy has an essential impact on surface generation and subsurface damage. In this work, the molecular dynamics method is applied to create the diamond nano-cutting models of Ni-based single crystal (NBSX) superalloy workpieces with different crystal orientations, and the surface/subsurface damage characteristics, crystal structure changes, cutting force, and atomic temperature and stress are discussed. The results show significant differences in surface/subsurface quality, crystal structure transformation, cutting force, atomic temperature and stress distributions and dislocation density obtained from nano-cutting workpieces along different crystal orientations. In four groups of workpieces, the surface/subsurface quality is used as an evaluation index, which shows that the [110](001) crystal orientation has the best cutting effect, and the [111](1‾ 10) crystal orientation is the worst cutting direction. This work reveals the damage generation mechanism of the machined surface/subsurface of NBSX superalloy on an atomic scale, which provides technical support for improving machining quality and optimizing machining parameters.