The construction of major hydropower projects globally is challenged by slope deformation in reservoir areas. The deformation and failure mechanisms of large rock slopes are complex and poorly understood, making prevention and management extremely challenging. In order to explore the influence mechanism of the water level variation on the deformation of steep toppling bedding rock slopes, this paper takes the right bank slope near the dam area of the Longtou Hydropower Station as an example, and field investigations, deformation monitoring, physical simulation tests and numerical analyses are carried out. It is found that the slope deformation response is obvious under the influence of the reservoir water level variation, which is mainly reflected in the change in the slope groundwater level, rock mechanical parameters and seepage field in the slope body. The toe of the slope produces plastic deformation and maximum displacement. With the increase in the reservoir water level, the plastic zone expands and the displacement increases, which leads to the intensification of the slope deformation. This paper puts forward that the deformation and failure modes of the steep and toppling bedding rock slope caused by water level variation are due to shear dislocation, bending deformation and toppling fracture. This study reveals the influence mechanism of the water level variation on the deformation of steep and toppling bedding rock slopes, which can provide theoretical support for the construction of major hydropower projects.