As the operation speed of China’s high-speed trains continues to increase, a variety of complex wheel wear problems continue to emerge. Many line tests show that the differential wheel wear of the motor car and trailer car is obvious. The aim of this paper is to explore the differential wear mechanism of motor cars and trailers and their effect on dynamic performance. Firstly, this paper established a high-speed train model, which consists of two motor cars and two trailers. Then the causes of differential wear of the high-speed train from the perspective of wheel-rail contact and wheel wear were analyzed, and the Jendel wear model was used for wheel wear prediction. The wear model was verified through measured wheel wear data. Lastly, the dynamic performance of the differential wear of the high-speed train was analyzed. The results showed that the different distribution of the adhesive sliding zone in the contact patch, the different wheel-rail normal force, and tangential forces are the reasons for the differential wear. The established dynamic model and wear model can effectively predict the differential wear of the motor cars and trailer, and the maximum wear depths of the motor car and the trailer wheel were 0.886 mm and 0.721 mm. This verified the validity of the simulation model. When wheel differential wear occurs, the overall dynamic performance of the trailer is superior to that of the motor cars.