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We identify evidence for three large paleo-earthquakes in central Switzerland with moment magnitudes (M > 6.5–7.0) significantly exceeding historically known values. These earthquakes occurred during the past 15 k.y. and were strong enough to simultaneously affect a large region that includes the present-day major cities of Lucerne and Zurich. We reconstruct the chronology, magnitudes, and epicenters of these prehistoric earthquakes using temporal and spatial correlation of multiple subaqueous landslide deposits in Lake Zurich and Lake Lucerne through high-resolution seismic surveys, radiocarbon-dated sediment cores, and spatial calculations using an empirical seismic attenuation model. Our data indicate ongoing Alpine deformation that generated and could potentially generate destructive events in heavily populated regions that have been unaccustomed to seismic activity during historic time.