Abstract: The friction process of the WC–Co cemented carbides in the different conditions was investigated by molecular dynamics simulation in this work. The effects of grain size, friction load, and sliding velocity on the friction and wear behavior of the cemented carbides were analyzed. The friction and wear microscopic mechanism of the cemented carbides in the atomic scale was revealed. The results show that, with the increase of grain size, the dislocation slip in the Co and WC phases gradually plays more important role in the friction-induced plastic deformation mechanism rather than the grain rotation. The increase of friction load may lead to the deformable Co bonding phase being extruded from the surface and removed first. Nonetheless, the extrusion-wear mechanism of the Co phase can be suppressed by reducing the WC grain size, and the sliding wear resistance of the cemented carbides can be improved. Besides, the increase of sliding rate may reduce the wear rate. The main reason is that, in the process of high-speed sliding, the nucleation and expansion of dislocation in each phase of the subsurface layer lacks the continuous driving stress, and the dislocation density is low. Therefore, WC is difficult to fracture, and the wear degree caused by Co phase being extruded from the surface is significantly reduced.