Abstract: In the hydro-fluctuation zones of clastic rock bank slopes, mudstone is subjected not only to dry-wet cycles but also to the persistent self-weight stress of overlying rock strata. To investigate the mechanical properties and energy evolution mechanisms of mudstone under coupled conditions, tests under the coupled action of multi-cycle stress and wet-dry cycles were conducted. The results show that: (1) The compressive strength and deformation parameters of mudstone exhibit a significant deterioration trend with increasing test cycles, with the deterioration rate being the fastest in the first 5 cycles, accounting for more than 70% of the total deterioration. The overlying stress has a significant promoting effect on the deterioration of mudstone's compressive strength. Under a stress of 0.6 MPa, the rock strength decreases by 28.8% compared to the stress-free state; (2) With the increase of test cycles, the total strain energy density, elastic energy density, and dissipated energy density of the specimens all present a decreasing trend, and the overlying stress exacerbates the deterioration of these three energy densities, with the three energy densities decreasing by 23.8%, 27.4%, and 4.8% respectively under a stress of 0.6 MPa compared to the stress-free state. (3) The results of microscopic tests indicate that the overlying stress promotes the development and penetration of fractures, which provides seepage channels for dry-wet cycles. The microscopic structure of mudstone is significantly damaged, gradually transforming from the initial dense structure to a disordered and loose one, thereby leading to the deterioration of mudstone mechanical properties. The research results are of reference value for the stability analysis of clastic rock bank slopes in the Three Gorges Reservoir area.