The success of laser communications heavily relies on the stiffness, dynamic properties, static performance, and manufacturability of the U-frame. The U-frame is a fundamental element in satellite-to-ground laser communication telescopes. However, there is currently a lack of research on the optimal design of U-frames, leading to a significant gap between ideal construction and practical manufacturability. To address these concerns, this study proposes a comprehensive approach that combines multi-objective topology optimization and multi-start size optimization techniques. This approach considers the multidisciplinary constraints imposed by mechanical, control, and optical systems. The objective is to achieve both the conceptual and detailed design of a novel U-frame, while also ensuring thorough consideration of the structure’s manufacturability during the optimization process. The prototype of the optimized U-frame was successfully fabricated using laser welding processes. The tensile test conducted on the prototype supported the idea that laser welding can enhance the micro-grain size of the joint, leading to improved overall mechanical properties. In particular, the joint strength achieved through laser welding was found to be 1.5 times greater than that achieved through TIG (Tungsten Inert Gas) welding. Additionally, the results obtained from the free vibration experiment closely aligned with the simulation, confirming the feasibility of manufacturing the optimized structure. The optimized structure demonstrated an improvement of 7.13% in dynamic performance and 29.61% in static performance compared to the first-generation structure. Additionally, there was a reduction of 29.89% in mass without affecting the remaining performance aspects. The successful fabrication of the prototype validates the feasibility of the proposed welding process and highlights the superiority of the new U-frame.