The train-bridge dynamic interaction problem began with the development of railway technology, and requires an evaluation method for bridge design in order to ensure the safety and stability of the bridge and the running train. This problem is studied using theoretical analysis, numerical simulation, and experimental study. In the train-bridge dynamic interaction system proposed in this paper, the train vehicle model is established by the rigid-body dynamics method, the bridge model is established by the finite element method, and the wheel/rail vertical and lateral interaction are simulated by the corresponding assumption and the Kalker linear creep theory, respectively. Track irregularity, structure deformation, wind load, collision load, structural damage, foundation scouring, and earthquake action are regarded as the excitation for the system. The train-bridge dynamic interaction system is solved by inter-history iteration. A case study of the dynamic response of a CRH380BL high-speed train running through a standard-design bridge in China is discussed. The dynamic responses of the vehicle and of the bridge subsystems are obtained for speeds ranging from 200 km·h−1 to 400 km·h−1, and the vibration mechanism are analyzed.