The dynamic model of a high-speed electric multiple unit (EMU) is established based on the theory of rigid-flexible coupling multi-body system dynamics. Depending on the actual operating conditions of the vehicle, there are a variety of conditions of car body load-time history. We assess ineffective amplitude omission, load spectrum extrapolation, and extreme determination through the car body load-time history, and then obtain the car body fatigue load block spectrum. Finally, we perform a fatigue strength test on the whole car body on a car body fatigue test bench. It is shown that the accelerations of the three directions of the vehicle car body increase with increasing speed. When the train passes a curve, the lateral acceleration average becomes greater. There is also an increase in the car body accelerations in three directions when the train goes through a turnout or twisted line. Under the condition of a failed spring, the vertical acceleration of the car body is obviously increased. Anti-yaw damper failure will cause a significant increase in vehicle lateral acceleration. The failure of lateral and vertical dampers on the second suspension causes an insignificant acceleration increase in three directions. The car body acceleration increases the wear-type profile relative to the original profile in various working and speed level conditions a little. The influence on the damage of vehicle car body under various working conditions is predicted according to the obtained load spectrum.