Through compound treatment of surface nanocrystallization and low-temperature ion sulfurization, the compound-modified layer (nanocrystalline/FeS film) with excellent friction-reduction and anti-wear properties was fabricated on the surface of AISI321 stainless steel. A comparative study is conducted on the element distribution, microstructure, and vacuum tribology properties (1 × 10‒4 Pa) of compound-treated samples, single-related samples (surface nanocrystallization or low-temperature ion sulfurization), and original substrate samples. The nanocrystallization treatment formed the high hardness, high activity nanocrystalline structure on the surface of AISI321, which results in significantly refined microstructure, increased thickness and concentration of S element in the compound-sulfurized layer compared to the single-sulfurized layer on the substrate. Tribological tests reveal that both the original AISI321 substrate and the single-sulfurizing treated samples are subject to severe abrasion. Single nanocrystallization treatment can improve the wear resistance of AISI321, while the compound treatment can obviously improve the comprehensive tribological properties with milder wear and lower friction of coefficient. The good tribological properties of the compound-modified layer are related to the enhancement of substrate hardness and the increase of the thickness, density, and homogeneity of the sulfurized layer. Furthermore, a physical model is developed for the vacuum tribological behavior of the samples after different treatments. This model provides a reference for revealing the tribological mechanism of the compound-modified layer treated by surface nanocrystallization assisted chemical heat treatment.