The need for the lightweight of special vehicle trailer frame is substantially growing due to high gasoline prices and serious environmental issues. In this study, we develop a new lightweight sub-frame for large container trailers and evaluate its durability through a fatigue test. To this end, a reliable three-dimensional parametric finite element model of a sub-frame is constructed and then an optimized lightweight sub-frame is newly developed by using the Taguchi method. Next, we make a trial product of the optimized lightweight sub-frame and conduct a driving test to identify the driving load history at vulnerable areas. Finally, we evaluate the durability of the developed lightweight sub-frame through a fatigue test based on the load history.