Three Pleistocene giant slope failures are observed in high-resolution bathymetric and seismic reflection data off Southern Chile, two of which extend across the full width of the continental slope from the shelf break to the trench. With mobilized volumes between 253 km3 and 472 km3, these slides are among the largest submarine landslides documented at active continental margins so far. Deposits of each of the slides are imaged as chaotic sequences in seismic reflection lines buried beneath well-stratified sediments in the Chile Trench. The ages of the three slides are about 0.25, 0.41 and >0.56 Ma. The main preconditioning factor for the slope instabilities seems to be local uplift of the continental slope that results in peculiarly high slope angles of up to 30°. Uplift of the marine and continental forearc of the study area is the result of shortening across upper plate faults and therefore a long-term continuous process. Slope instability seems to be an iterative process and failure is likely to recur.