Friction phenomena are strongly affected by interfacial mechanical and tribochemical effects, which involve major factors such as loads, sliding rates, sliding times, humidity, temperatures, and oxide films. For practical applications at different vacuum levels, friction mechanisms (adhesive wear, abrasive wear, fatigue wear, corrosive wear, and micromotor wear) are highly important for the development of advanced materials with desirable tribological properties to promote vacuum tribology. In this review, in combination with the current understanding of friction‒wear interactions, the tribological phenomena caused by changes in the surfaces of friction pairs that are highly dependent on complex conditions in different vacuum environments are analyzed and summarized. Subsequently, protection strategies for different structural materials are summarized. Finally, this work provides an outlook for designing advanced and sustainable protective materials under different vacuum conditions.