As the number of large reservoirs has grown rapidly, drawdown of water level has become a major factor in inducing landslides. A new simulator was developed to simulate the in-flight drawdown in a centrifuge model test. A series of centrifuge model tests was conducted on slopes with different gradients under drawdown conditions. The failure mechanism was obtained via an integrated analysis of deformation and failure processes according to the displacement histories of the slopes measured by the image capture and displacement measurement system. The slip surface, with slippage failure, was developed from the top downwards due to the drawdown. The displacement histories of the sliding body could be divided into three stages with the increase rate changing from small to large and finally becoming negligible. The deformation of the slope only appeared within a limited zone with a nearly invariable boundary surface during the drawdown. The boundary surface moved closer to the slope surface with the deceasing slope gradient. The drawdown caused a significant coupling process of local failure and deformation localization, which developed from the upper part to the lower part. The upper part of the sliding body behaved as a rigid body, and the lower parts exhibited significant deformation after the slip surface formed, which should be reasonably captured in a stability analysis of a slope under drawdown conditions.