Abstract: The next-generation reusable space vehicles undergo multiple flight-reentry cycles throughout their entire service life, during which they are subjected to extreme aerodynamic, thermal, mechanical, and vibrational loads. These loads involve complex multi-physics interactions, including severe transient thermo-mechanical coupling. The mechanical behavior and damage failure mechanisms of fiber-reinforced ceramic matrix composites (CMC) under such extreme conditions need to be clearly understood. This study investigates the damage evolution mechanisms of CMC thermal structures in cyclic service environments from the perspective of multi-physics coupling. It identifies transient thermo-mechanical loads as one of the primary factors influencing performance degradation under repeated use conditions. A comprehensive predictive and analytical framework for thermomechanical-induced cracking under high-temperature transient large thermal gradients is proposed. By developing a coupled thermal conduction-mechanical response model, we achieve quantitative characterization of the spatiotemporal evolution of the internal temperature field, stress field, and crack energy release rate (ERR) in the material. The results indicate that the non-uniform temperature gradients caused by transient thermal loads are the primary drivers of subsurface stress state reversal (tension-compression conversion). This, in turn, interacts with the material microstructure, leading to the maximum ERR occurring in the subsurface region on the windward side. Furthermore, bending constraints can double the peak ERR compared to unconstrained conditions. Based on parametric analysis, design guidelines for repeatable use, focusing on low ERR, are proposed. These guidelines highlight the optimization directions for CMC thermal structures, including gradient modulus, high thermal conductivity, low thermal expansion, and thin-walled designs. Experimental validation using a 1500 °C/1.5kN thermomechanical test platform demonstrates that the C/SiC ceramic matrix composite-wing leading-edge (CMC-WLEs) thermal structure maintains its integrity after over ten cycles of loading, with no delamination or matrix cracking detected through nondestructive testing. This study offers an innovative theoretical-experimental methodology for the synergistic optimization of materials and structures in reusable CMC thermal structures and damage-tolerant design, which is of significant engineering importance for overcoming the design challenges in hypersonic vehicle thermal protection systems.