In order to reduce the wheel profile wear of highspeed trains and extend the service life of wheels, a dynamic model for a high-speed vehicle was set up, in which the wheelset was regarded as flexible body, and the actual measured track irregularities and line conditions were considered. The wear depth of the wheel profile was calculated by the well-known Archard wear law. Through this model, the influence of the wheel profile, primary suspension stiffness, track gage, and rail cant on the wear of wheel profile were studied through multiple iterative calculations. Numerical simulation results show that the type XP55 wheel profile has the smallest cumulative wear depth, and the type LM wheel profile has the largest wear depth. To reduce the wear of the wheel profile, the equivalent conicity of the wheel should not be too large or too small. On the other hand, a small primary vertical stiffness, a track gage around 1,435-1,438 mm, and a rail cant around 1:35-1:40 are beneficial for dynamic performance improvement and wheel wear alleviation.