In order to analyze the influence of uneven road surface, unsprung mass and vibration generated by the coupling of unbalanced electromagnetic force and road excitation on the vibration response of a vehicle driven by in-wheel motors, a multi-rigid body dynamic model of a four-wheel motor driven vehicle is established by Adams/Car. The vertical dynamics simulation is carried out to analyze the vehicle vibration response under different influence factors. The results show that the influence of change in motor driving mode on vehicle ride comfort is related to the sprung mass. When the sprung mass is large, the relative dynamic load of the tire is mainly affected by the motor driving mode, while other vehicle ride comfort evaluation indexes are little affected by it. The vehicle vibration response is significantly deteriorated by the deterioration of road roughness and the increase of vehicle speed. The relative dynamic load of the wheel and the eccentricity of the stator and rotor of the hub motor are significantly increased by the increase of unsprung mass, which adversely impacts the safety of the wheel. Vehicle vibration response is little affected by unbalanced electromagnetic force.