Numerous industries are concerned by the humanitarian, environmental, and economic consequences of debris flows, landslides, and material run-outs. However, the run-out behavior following a loss of confinement, e.g., dam failure, is not well understood. The material’s complex constitutive behavior means multiple mechanisms contribute to the deformation, e.g., slope instability, seepage forces, erosion, or static liquefaction. In this study, centrifuge models of fly ash deposits, with varying initial deposit density and water table height, were subjected to a rapid loss of lateral confinement. Deformation, pore pressure, and water content measurements were used to investigate and separate the mechanisms governing the run-out. Static liquefaction was observed in deposits initially looser than the critical state and led to a rapid material outflow. Slope instability was the initial failure mechanism for denser deposits or those with reduced water tables, with transient stability due to dilation-induced negative excess pore pressures followed by progressive failures caused by seepage pressures from drainage and pore pressure dissipation. Cone penetration tests, performed before the loss of confinement at different penetration rates, were used to characterize the material run-out and volume change tendencies and demonstrate a practical tool for assessing the run-out risk of deposits in the field.