In order to analyze the influence of evolution of the dominant order of wheel polygonal wear on the vibration response of the train-bridge coupling system, the key influencing factors and evolution patterns of the dominant order of polygon wear were summarized first. Meanwhile, the coupled dynamic model of the train-bridge system was established by utilizing a combined simulation approach with ANSYS and SIMPACK. Subsequently, the impact of evolution of the dominant order of wheel polygonal wear on the vibration response of the train-bridge coupled system under different operational mileages, train operating speeds, vertical stiffness of fasteners, and variations in wheel diameter, was explored. The research results indicate that the evolution of the dominant order of wheel polygonal wear significantly affects the dynamic response of the train-bridge coupled system. In general, when the wheels experience high-order polygonal wear, the lateral and vertical accelerations at the mid-span of the bridge increase significantly. Moreover, the wheel-rail force and derailment coefficient also increase significantly, with the train wheels experiencing momentary bouncing. This has an impact on both the quality of high-speed train operation on the bridge and the safe operation of the bridge structure, necessitating timely wheel re-profiling.