To better improve the lightweight and fatigue durability performance of the tractor cab, a multi-objective lightweight design of the cab was carried out in this study. First, the finite element model of the cab with counterweight loading was established and then confirmed by the physical testing, and use the inertial relief method to obtain stress distribution under unit load. The cab-frame rigid-flexible coupling multi-body dynamics model was built by Adams/car software. Taking the cab airbag mount displacement and acceleration signals acquired on the proving ground as the desired signals and obtaining the fatigue analysis load spectrum through Femfat-Lab virtual iteration. The fatigue simulation analysis is performed in nCode based on the Miner linear fatigue cumulative damage theory. Then, with the mass and fatigue damage values as the optimization objectives, the bending-torsional stiffness and first-order bending-torsional mode as constraints, the thickness variables are screed based on the sensitivity analysis. The experimental design was carried out using the Optimal Latin hypercube method, and the multi-objective optimal design of the cab was carried out using the Kriging approximation model fitting and particle swarm algorithm. The weight of the optimized cab is reduced by 7.8% on the basis of meeting the fatigue durability performance. Finally, a seven-axis road simulation test rig was designed to verify its fatigue durability. The results show the optimized cab can consider both lightweight and durability.