In recent years, many hill flattening and gully filling projects are carried out in the northwest of China to create land for construction. These projects have formed a number of loess fill slopes, which are prone to failure induced by rainfall. However, the failure mechanism of loess fill slope is not clear under rainfall conditions. In this study, a flume model experiment is carried out to reveal the characteristics and mechanism of failure loess fill slopes. The volumetric water content, soil pressure, and pore water pressure are analyzed to investigate the effect of rainfall infiltration on fill slope. The results shown that rain-induced failure mode of loess fill slopes exhibited progressive multi-stage sliding characteristics, including slope toe failure, crack development and penetration, local sliding, and overall misaligned sliding stages. The influence of the weak interface between the fill slope and the bedrock/natural slope on slope damage was revealed based on the hydromechanical characteristics. It is shown that the maximum migration rate of wetting front along the weak interface is about 5 times that in loess fill, and the weak interface becomes the dominant channel controlling the hydrological characteristics of the slope, accelerating the saturation of the fill loess slope and generating seepage forces towards the outside of the slope, causing the loess fill slope prone to shear slide along with weak interface. Therefore, we believe that the weak interface between the fill slope and the bedrock/natural slope surface plays an important role in slope failure.