The bank slope of the Three Gorges Reservoir is affected by seasonal water level fluctuations, which leads to deterioration of the rock mass, resulting in a series of geological disasters such as landslides and mudslides. Therefore, in order to thoroughly understand the degradation mechanism of mechanical characteristics under wetting-drying cycles, uniaxial compression tests and triaxial compression tests were used to reveal the relationship between mechanical characteristics and wetting-drying cycles. Uniaxial compression tests results show that with the number of wetting-drying cycles increases, the mechanical characteristics show a decreasing trend, and the compaction stage of the sample increases significantly. It was found that the first 10 wetting-drying cycles have a greater impact on the mechanical characteristics of red sandstone under the triaxial compression condition, the mechanical parameters such as deviatoric stress, elasticity modulus dropped rapidly under the first 10 cycles and then tend to be stable. Based on the testing data under wetting-drying cycle condition, the mechanical parameters of the statistics damage constitutive model were modified and the results show that the modified damage constitutive model has a high degree of fit with the test data, indicating that the modified mechanical parameters can better reflect the degradation of red sandstone after the wetting-drying cycles. This understanding of the degradation process of the mechanical characteristics under wetting-drying cycles can provide theoretical guidance for the protection of dangerous slopes in the drawdown zone of the Three Gorges Reservoir.