Numerical tsunami simulations indicate that only the combination of flank movement followed by an explosive eruption can explain historical eyewitness accounts. This movement is consistent with depressurization of the magma feeding system, causing a catastrophic explosion. Here we show, based on three-dimensional seismic data, that ~1.2 km³ of Kolumbo’s northwestern flank moved 500–1000 m downslope along a basal detachment surface. However, the source mechanisms behind the tsunami have been disputed due to difficulties in sampling and imaging submarine volcanoes. The 1650 eruption of the Kolumbo submarine volcano triggered a tsunami causing major destruction on surrounding islands in the Aegean Sea. Tsunami generation during volcanic eruptions is complex and often due to a combination of processes. Volcanic eruptions can trigger tsunamis, which may cause significant damage to coastal communities and infrastructure.