In the aerospace industry, spacecraft often serve in harsh operating environments, so the design of ultra-lightweight and high-performance structures is a major requirement in aerospace structure design. In this article, a lightweight aerospace bracket considering fatigue performance was designed by topology optimization and manufactured by 3D-printing. Considering the requirements of assembly with a fixture for fatigue testing and avoiding stress concentration, a reconstructed model was presented by CAD software before manufacturing. To improve the fatigue performance of the structure, this article proposes the design idea of abstracting the practiced working condition of the bracket subjected to cycle loads in the vertical direction via a multiple load-case topology optimization problem by minimizing compliance under a variety of asymmetric extreme loading conditions. Parameter sweeping was used to improve the computational efficiency. The mass of the new bracket was reduced by 37% compared to the original structure. Both numerical simulation and the fatigue test were implemented to support the validity of the new bracket. This work indicates that the integration of the proposed topology optimization design method and additive manufacturing can be a powerful tool for the design of lightweight structures considering fatigue performance.