The Pleistocene opening of the endorheic Duero River drainage basin (northwestern Spain and central Portugal) has led to river incision, creation of steep valley sides, and development of large (>0.1km2) and episodically active rotational and roto-translational landslides along river reaches where a weak geological lithology has been exposed by river erosion. These landslides occur in the central part of the Duero basin despite low precipitation, weak contemporary seismicity, and low regional relief. These landslides occurred as a result of the downcutting of the Duero River and its tributaries through a sequence of Miocene basin-fill sediments. In the last few thousand years the incision reached a series of high-plasticity, low-strength clay layers within the sedimentary sequence. Owing to this mechanism, these landslides occurred in a specific area at a specific period of time. All of the large landslides are located at the outside of meander bends, suggesting that river lateral erosion facilitated slip failures. Recent anthropogenic activities to control river flows and to stabilize river banks have decreased the possibility of future landslides in this area.