Large landslides (>0.1 km2) are important agents of geomorphic change. While most common in rugged mountain ranges, large landslides can also be widespread in relatively low-relief (several 100 m) terrain, where their distribution has been relatively little studied. A fuller understanding of the role of large landslides in landscape evolution requires addressing this gap, since the distribution of large landslides may affect broad regions through interactions with channel processes, and since the dominant controls on landslide distribution might be expected to vary with tectonic setting. We documented >400 landslides between 0.1 and ∼40 km2 across ∼140,000 km2 of eastern Oregon, in the semiarid, southern interior Columbia River basin. The mapped landslides cluster in a NW-SE–trending band that is 50–100 km wide. Landslides predominantly occur where even modest local relief (∼100 m) exists near key contacts between weak sedimentary or volcaniclastic rock and coherent cap rock. Fault density exerts no control on landslide distribution, while ∼10% of mapped landslides cluster within 3–10 km of mapped fold axes. Landslide occurrence is curtailed to the NE by thick packages of coherent basalt and to the SW by limited local relief. Our results suggest that future mass movements will localize in areas stratigraphically preconditioned for landsliding by a geologic history of fluviolacustrine and volcaniclastic sedimentation and episodic capping by coherent lava flows. In such areas, episodic landsliding may persist for hundreds of thousands of years or more, producing valley wall slopes of ∼7°–13° and impacting local channels with an evolving array of mass movement styles.