With the increase in the occupancy ratio of bridges and the speed of trains, the probability of trains being located on bridges during earthquakes increases, and the risk of derailment increases. To investigate the influence of unequal-height piers on the dynamic response of high-speed railway train bridge systems, a seismic action model of high-speed train–track–bridge dynamic systems was established based on the in-house code using the finite element method and multi-body dynamics method. It is found that (1) compared to equal-height piers, the peak lateral dynamic response of unequal-height piers (with gradually increasing pier heights) decreases, while the peak vertical dynamic response increases; (2) the peak lateral dynamic response of unequal-height piers (with a steep increase in pier height) increases sharply, while the peak vertical dynamic response decreases; and (3) the safety indicators of equal-height piers are significantly superior to the two unequal-height pier operating conditions.