Heavy duty tractor plays a vital role in traffic transport industry, in roads and building construction. In all of these applications, the structural failure of vehicle is the key issue in the process of safe running. This paper is devoted to the investigation of dynamic characteristics and fatigue reliability for the heavy duty tractor. Appling the non-similar substructure modeling technology, the novel integrated simulation model of heavy duty tractor is established. The total number of elements of the simulation model are reduced obviously from 4,380,449 to 117,065. A complete experimental process, which contains selecting digital acquisition module, the layout of sensors, the data processing, etc., is presented. The validity of the analysis method and the simulation model is verified by comparing with experimental results. The analysis methods of the random frequency domain and the multiaxial fatigue are employed to obtain the fatigue damage samples of heavy duty tractor. Meanwhile, the influences of confidence, pre-stress field and channel correlation on reliability are discussed. Moreover, on the basis of the system reliability distribution, the reliability of determined life and the index of B10 life are assessed. This study gives a reference for avoiding the structural failure and enhancing the system safety.