Ultra-low friction is crucial for the anti-friction, anti-wear, and long-life operation of nanodevices. However, very few two-dimensional materials can achieve ultra-low friction, and they have some limitations in their applications. Therefore, exploring novel materials with ultra-low friction properties is greatly significant. The emergence of ternary two-dimensional materials has opened new opportunities for nanoscale ultra-low friction. This study introduced nickel phosphorous trisulfide (NiPS3, referred to as NPS), a novel two-dimensional ternary material capable of achieving ultralow friction in a vacuum, into the large nanotribology family. Large-size and high-quality NPS crystals with up to 14 mm × 6 mm × 0.3 mm dimensions were grown using the chemical vapor transport method. The NPS nanosheets were obtained using mechanical exfoliation. The dependence of the NPS nanotribology on layer, velocity, and angle was systematically investigated using lateral force microscopy. Interestingly, the coefficient of friction (COF) of NPS with multilayers was decreased to about 0.0045 under 0.005 Pa vacuum condition (with load up to 767.8 nN), achieving the ultra-low friction state. The analysis of the frictional dissipation energy and adhesive forces showed that NPS with multilayers had minimum frictional dissipation energy and adhesive forces since the interlayer interactions were weak and the meniscus force was excluded under vacuum conditions. This study on the nanoscale friction of a ternary two-dimensional material lays a foundation for exploring the nanoscale friction and friction origin of other two-dimensional materials in the future.