Loess is a Quaternary aeolian sediment that has been deposited over an undulating bedrock landscape, forming the Chinese Loess Plateau. Where this bedrock comprises mudstones, the loess-bedrock interface conditions the landscape in a state of high landslide susceptibility. In this neo-tectonically active region, earthquakes and rainfall are highly likely to act as triggers. This study focuses on a representative loess-mudstone interface landslide located on a hillside behind the Vehicle Management Office in Wuqi County, Yan'an City, Central China, to investigate the coupled effects of rainfall infiltration and seismic loading on slope deformation and failure mechanisms. Numerical simulations were developed to better understand how co-seismic landslides are affected by different rainfall conditions, and how this resulted in different mechanisms of failure and runout. The results show that rainfall infiltration progressively weakens the mudstone layer, leading to the upward extension of the potential slip zone and a marked reduction in slope stability. Under subsequent seismic loading, deformation is concentrated along the loess-mudstone contact, and topographic amplification further increases peak ground acceleration at the slope crest. The interaction between rainfall-induced softening and seismic excitation significantly accelerates slope failure, highlighting the critical control of the mudstone layer's post-softening strength on overall stability. The findings of this study provide a valuable reference for analyzing the disaster mechanisms of similar loess landslides.