As an important machine for agricultural application, the upland gap self-propelled sprayer is environmental friendly and operates efficiently. In this paper, the chassis frame, which is one of the important components of the sprayer, is studied and a disconnected longitudinal beam frame with an X-shaped reinforcement beam was designed. The static mechanical properties of the frame under bending, torsion, emergency braking and emergency turning conditions are analyzed by a finite element method, and the optimization idea was proposed. On this basis, the topology optimization method was applied to optimize the crossbeam and the reinforcement beam positions, resulting in a 2.2% reduction in the overall mass of the frame, a 19.4% reduction in the maximum deformation while maintaining a small change in the maximum stress in the bending condition, and a 4.1% and 15.1% reduction in the maximum deformation and maximum stress of the frame in the torsion condition, respectively. The frame section width and thickness parameters were optimized by multi-objective driven optimization. The results showed that the frame mass and maximum stress were reduced by 6.8% and 1.9%, respectively, in the bending condition at the cost of a slight increase in frame deformation.