Historic records indicate that structures built in and around the two harbours of Alexandria, Egypt, were periodically damaged by powerful events such as earthquakes and tsunamis. This geoarchaeological study reveals that human activity in nearshore and port settings has also triggered sediment deformation and construction failure. Analysis of radiocarbon-dated Holocene cores and submerged archaeological excavations record a significant incidence of sediment destabilization and mass movement in the ports since human occupation in the 1st millennium B.C. Anthropogenic substrate failure is documented from about the time of the city’s founding by the Greeks in the 4th century B.C. to the present. Construction on unconsolidated sediment substrates was a factor of sediment destabilization, at times in conjunction with earthquakes, storm waves and tsunamis. Engineer reports on port construction during the past century, however, show substrate failure can also occur by building and other human activity, independently of high-energy natural events. Some recent failure and associated mass flows in the harbours were triggered by loading effects associated with emplacement of large structures on weak, water-saturated substrates. Slumps, debris flows and mudflows, initiated by substrate destabilization, caused lateral displacement of sediment and construction debris for tens of meters away from construction sites. Human-induced processes that triggered sediment failure in the ports from Greek to recent time are not likely to be unique to this sector, and findings here may help explain how some sites in coastal settings elsewhere were submerged.