The probability that an earthquake occurs when a train is running over a bridge in earthquake-prone regions is much higher than before, for high-speed railway lines are rapidly developed to connect major cities worldwide. This paper presents a finite element method-based framework for dynamic analysis of coupled bridge–train systems under non-uniform seismic ground motion, in which rail–wheel interactions and possible separations between wheels and rails are taken into consideration. The governing equations of motion of the coupled bridge–train system are established in an absolute coordinate system. Without considering the decomposition of seismic responses into pseudo-static and inertia-dynamic components, the equations of motion of the coupled system are formed in terms of displacement seismic ground motions. The mode superposition method is applied to the bridge structure to make the problem manageable while the Newmark-β method with an iterative computation scheme is used to find the best solution for the problem concerned. Eight high-speed trains running over a multi-span steel truss-arch bridge subject to earthquakes are taken as a case study. The results from the case study demonstrate that the spatial variation of seismic ground motion affects dynamic responses of the bridge–train system. The ignorance of pseudo-static component when using acceleration seismic ground motions as input may underestimate seismic responses of the bridge–train system. The probability of separation between wheels and rails becomes higher with increasing train speed. Copyright © 2011 John Wiley & Sons, Ltd.