Atomically thin lubrication materials with anti-friction properties are crucial for reducing energy consumption and extending the service life of micro/nanoelectromechanical systems (MEMS/NEMS). However, achieving atomically thin films with ultra-low friction properties at the atomic/nanoscale even at the micrometer scale presents significant challenges. In this study, large-size and high-quality monolayer MoS2 (ML MoS2 ) was grown on SiO2 /Si substrate by chemical vapor deposition (CVD) method. Compared with mechanically exfoliated ML MoS2 , the CVD-grown ML MoS2 (CVD-MoS2 ) exhibits an ultra-lower friction coefficient (0.009 04). Based on the stick–slip effect and Prandtl–Tomlinson (P–T) model, the reduction of puckering effect indicates stronger interaction and lower interface potential barrier in tip, CVD-MoS2 , and SiO2 /Si substrate system. Moreover, combining with the density functional theory calculations, the stronger interface adhesion and higher overall charge redistribution degree of CVD-MoS2 can also be used to explain its ultralow friction state. This work will provide theoretical guidance for designing ultra-thin lubricating materials with ultra-low friction properties.