Bridges represent a significant proportion of high-speed railway (HSR) lines in China, and high-speed trains operate on these structures for prolonged periods. Consequently, the occurrence of an earthquake during a train crossing is a probable event. With the support of the existing communication technology, the train will receive a warning in advance and brake urgently when the earthquake hits the train. However, research on the response of high-speed trains traversing bridges during an earthquake is scarce. To address this research gap, a three-dimensional train-track-bridge coupled braking system (TTBCBS) is developed using the finite element method and multibody dynamics, and the system’s motion equation is derived. Furthermore, the system is then programmed using mathematical software, and dynamic analysis is performed using different parameters such as friction coefficient and pier height under train braking and earthquake. Finally, the calculated train and bridge responses are evaluated based on safety indices, which provide evaluation standards for train running safety (TRS). However, it is found that the response of both the train and the bridge is smaller when the train is braking under earthquake, which is advantageous for the response of the TBCBCS system.