Changes in wheel profiles considerably impact vehicle dynamics and ride safety, especially running stability. Due to inevitable wheel wear, a common maintenance practice is to periodically re-profile wheels according to their original profiles. The influence of the difference in the vehicle wheel shape on the wheel–rail contact behavior cannot be neglected. In this study, the influence of wheel profile changes on vehicle dynamics is investigated by integrating periodic wheel profile measurements with vehicle-track dynamic simulations. Moreover, on the basis of measured dynamic data of trains, time-frequency analysis is performed to study the distribution characteristics of vehicle dynamics. The results indicate that there are obvious energy peaks in the dynamic response of the abnormal vibration section along the operating direction. The differences in the profiles of each wheel on a vehicle can cause significant changes in the wheel–rail contact behavior. Furthermore, the evolution of the profile of the re-profiled wheel affects the dynamic response of the vehicle. Therefore, the evolution of each wheel profile should be considered for a detailed dynamic assessment of a vehicle in service.