The Messinian salinity crisis (MSC) - the most abrupt, global-scale environmental change since the end of the Cretaceous - is widely associated with partial desiccation of the Mediterranean Sea. A major open question is the way normal marine conditions were abruptly restored at the end of the MSC. Here we use geological and geophysical data to identify an extensive, buried and chaotic sedimentary body deposited in the western Ionian Basin after the massive Messinian salts and before the Plio-Quaternary open-marine sedimentary sequence. We show that this body is consistent with the passage of a megaflood from the western to the eastern Mediterranean Sea via a south-eastern Sicilian gateway. Our findings provide evidence for a large amplitude drawdown in the Ionian Basin during the MSC, support the scenario of a Mediterranean-wide catastrophic flood at the end of the MSC, and suggest that the identified sedimentary body is the largest known megaflood deposit on Earth.