According to the consideration of safe use, the design of tractor driving axle housing is too conservative, with its strength failing to demonstrate. Aiming at the lightweight design of the axle housing, this paper proposes a design method to ensure the reliability and robustness of the axle housing on the basis of realizing the lightweight. Firstly, based on the analysis of the natural frequency of the axle housing, the finite element model is verified, and the resonance phenomenon is analyzed. Secondly, the optimal area of axle housing is determined by the results of variable density topology optimization and the fatigue accumulation damage theory. In the optimized area, the shell thickness variables are selected by sensitivity analysis. Thirdly, based on the radial basis function (RBF) approximate model, a six-sigma robust optimization algorithm is adopted to optimize the axle housing with mass, equivalent stress, displacement and safety factor as the objective function. The simulation results show that the design variables, strength, stiffness and safety factor of the optimized drive axle housing reach 8σ level, and the mass of the axle housing decreases by 9.7%. Moreover, compared with the deterministic optimization design based on genetic algorithm, the safety factor, strength and stiffness of the bridge housing through the proposed method can be improved relatively while achieving the goal of lightweight, and meanwhile it provides a technical reference for the structural lightweight design of vehicles and other machineries.