Exploring the wear mechanisms of tribo-pairs is essential to reducing friction and wear. Although it has been known that the wear mechanisms between reciprocating sliding motion (RSM) and unidirectional sliding motion (USM) are different, the differences are seldom reported, which causes trouble for many researchers in selecting proper tribo-pairs or wear test methods. Herein, we systematically explore the effect of RSM and USM on the wear mechanism for several typical friction and lubricant materials, such as alloys, liquids, and solid lubricants. It is found that tribo-pairs suffer unstable sliding under RSM, and sliding speed as well as sliding direction change frequently, which makes it difficult to form a transfer layer or tribo-chemical reaction film, leading to high friction and abrasive wear for hard alloys and DLC coating. Additionally, the quasi-static stage under RSM, when lubricated with polyalphaolefin (PAO) 40, does not facilitate elastohydrodynamic (EHD) lubrication, which typically prevents wear. However, stable sliding under USM could lead to adhesive wear, increasing the friction coefficient for soft TC4 alloys. Although wear under RSM is generally higher than that under USM, increasing the applied load could diminish the wear difference for hard metals.