The relationship between subgrade settlement and rail deformation remains unclear, and the impact of subgrade settlement on dynamic responses of the ballasted track, as well as on the running safety and comfort of high-speed trains, has not been adequately quantified. To address such deficiency, a three-dimensional (3D) numerical model of train-ballasted track-subgrade coupled system considering spatial differential subgrade settlements was established. An innovative iterative algorithm was proposed to determine the real-time track-subgrade contact, enabling the analysis of resulting track irregularities and train-induced vibration. The results show that the number of unsupported sleepers increases with greater settlement amplitudes and shorter settlement wavelengths, while spatial differential subgrade settlement significantly affects wheel-rail interaction. Track structures located at the settlement center area on the side with less settlement, as well as those at the settlement boundary area on the side with greater settlement, are more susceptible to damage. These areas also exhibit higher dynamic vertical subgrade stress, thus aggravating differential settlement. The findings could provide theoretical basis and technical guidance for improving high-speed railway operation and maintenance practices. ... Read more