Early inhabitants along the hyperarid coastal Atacama Desert in northern Chile developed resilience strategies over 12,000 years, allowing these communities to effectively adapt to this extreme environment, including the impact of giant earthquakes and tsunamis. Here, we provide geoarchaeological evidence revealing a major tsunamigenic earthquake that severely affected prehistoric hunter-gatherer-fisher communities ~3800 years ago, causing an exceptional social disruption reflected in contemporary changes in archaeological sites and triggering resilient strategies along these coasts. Together with tsunami modeling results, we suggest that this event resulted from a ~1000-km-long megathrust rupture along the subduction contact of the Nazca and South American plates, highlighting the possibility of Mw ~9.5 tsunamigenic earthquakes in northern Chile, one of the major seismic gaps of the planet. This emphasizes the necessity to account for long temporal scales to better understand the variability, social effects, and human responses favoring resilience to socionatural disasters.