The problem of seepage erosion is widespread in occurrence, but is rarely recognized as one of landslide causes. This paper describes and explains one event of slope erosion in Jianghan plain and is focused on the role of seepage erosion. The laboratory test is performed to reconstruct the hydraulic processes leading to slope failure with the application of different hydraulic loads. The observation and measurement reveal that slope alteration experienced three stages under seepage, and hydraulic gradient played a key role during seepage erosion phase. Using these results, a CFD-DEM model is developed to investigate how the seepage-induced soil particle migration would affect the slope evolution. The geotechnical properties control the failure processes and cause a significant change to the toe erosion and loosened zone. Although the instability of slope is mainly attributed to seepage gradient force, the occurrence of seepage erosion affects the failure mode. This work provides new guidance for hydrodynamic landslide prevention.