To investigate the mechanical properties and damage evolution law of layered shale under varying moisture contents, we conducted triaxial compression experiments on rock samples with different bedding angles and moisture levels. This study analyzed the variations in mechanical properties of layered shale under different conditions, and established a predicted model for elastic modulus based on different bedding angles and moisture content. Additionally, the damage constitutive model of layered shale was improved. The study revealed that shale’s mechanical properties display anisotropy, which is influenced by the bedding angles and moisture contents. The elastic modulus of the rock increases with the rise of bedding angle, exhibiting a ‘U’-shaped change. Conversely, the mechanical properties of rocks deteriorate, and their brittleness weakens with the increase in moisture content. When the confining pressure increased, the overall mechanical properties of shale were enhanced, and the influence of bedding on shale was weakened, but the deteriorating effect of water on rocks was hardly affected. Based on the above experiments, a predicted model of equivalent elastic modulus of shale considering the coupling effect of bedding and different moisture contents was proposed, which could effectively predict the elastic modulus of layered shale with different moisture content under different confining pressures. Furthermore, based on the predicted model of elastic modulus, an improved damage constitutive model of layered shale under triaxial loading was established, and the damage accumulation trend of layered shale was obtained, which showed an “S”-shaped change with strain. Under the coupling effect of bedding and different moisture contents, the damage of shale was advanced, but the accumulation rate of damage slowed down. With the increase of confining pressure, the influence of bedding and moisture content on the damage characteristics of shale decreased, and the damage curves under different conditions gradually tended to isotropy. The developed damage constitutive model for layered shale under different moisture contents provides theoretical support for the study of reservoir fracturing and wellbore stability.