The soft interlayer and rock structure play a significant role in controlling the deformation of the bedding slope, and it is necessary to consider the phenomenon of the sudden change of local response in these key parts under rainfall conditions, and then to clarify the mechanism of rainfall infiltration and damage mechanism of such slopes. In this paper, a large red-layered flat-dipping bedding landslide was selected as the research object, and numerical calculations based on the Van Genuchten model for saturated–unsaturated flow were performed in order to investigate the hydrological response and distribution patterns of water within the slope during rainfall. Moreover, stability analysis was performed based on the seepage field results and secondary development of FLAC3D, and the landslide evolution process was simulated and reproduced using the constitutive model of double-variables and the strength reduction method (SRM). The results showed that the effects of heavy rainfall on the water distribution and stability of the highway slope are significant, while the effects on the natural slope are not significant. There are three phases of the slope destabilization: flexure and uplift state, deformation exacerbation state and shear failure state. The slope destabilization mechanism is a typical “sliding-bending-shearing” type. The results of the study can provide a theoretical basis for the study of the seepage, stability analysis and destabilization mechanism of bedding slopes.