The impact-sliding wear behavior of steam generator tubes in nuclear power plants is complex owing to the dynamic nature of the mechanical response and self-induced tribological changes. In this study, the effects of impact and sliding velocity on the impact-sliding wear behavior of a 2.25Cr1Mo steel tube are investigated experimentally and numerically. In the experimental study, a wear test rig that can measure changes in the impact and friction forces as well as the compressive displacement over different wear cycles, both in real time, is designed. A semi-analytical model based on the Archard wear law and Hertz contact theory is used to predict wear. The results indicate that the impact dynamic effect by the impact velocity is more significant than that of the sliding velocity, and that both velocities affect the friction force and wear degree. The experimental results for the wear depth evolution agree well with the corresponding simulation predictions.