A large-scale rockslide, developed from a deep-seated toppling failure, occurred in October 2018 following reservoir impoundment in the upper Lancang River, Southwest China. The evolution of this slope failure was investigated to reveal the instability mechanism of the rockslide after impoundment. Electron spin resonance (ESR) dating was used to determine the formation period of the toppling failure. Detailed field investigations, including joint measurements and surface, borehole and adit surveys, revealed the surface and subsurface features of the deformed rock masses. The Universal Distinct Element Code (UDEC) was used to simulate the evolutionary process of the slope failure. The results show that the toppling deformation rate accelerated with river downcutting and decreased after the modern valley formed. After reservoir impoundment, the mode of slope deformation transformed from creep toppling to rapid sliding. The sliding progressed upslope due to shear failure at the slope toe. In addition, the results of a series of simulations show that the action of tectonic stress can significantly increase the depth of toppling deformation. The investigation results imply that the evolution of the slope failure included five stages: initial deformation, accelerating deformation, creep deformation, formation of a throughgoing sliding surface and failure. The first three stages were dominated by toppling, whereas sliding dominated the latter two stages. Toppling was induced by river downcutting and promoted by the effects of tectonic stress and gravity. Reservoir impoundment promoted sliding at the slope toe, which induced upslope propagation of sliding above the toppling hinge surface. Once the slip zone coalesced with the shear failure surface at the front of the slope, the main rockslide occurred.