The performance of the rear axle plays an important role in the performance of vehicle, and its fatigue durability is an integral part in the vehicle development. Taking a SUV model as the research subject, a new methodology of multi-channel spindle coupled road simulator and fatigue simulation analysis for rear axle assembly was introduced in the paper, aiming to address the fatigue design and its verification for the rear axle in the development phase. Firstly, road loads in the proving ground was collected by arranging proper sensors. Secondly, physical iteration was performed on the multichannel spindle coupled road simulator by taking six component forces at the wheel hub as the target signals. Then, after the time waveform replication of the loads the durability test was conducted. Finally, the validated simulation model was successfully implemented to improve the fatigue life of the axle.