In the Ionian Sea, one of the most seismically active regions in the Mediterranean, subduction is commonly associated with uplift of coastal mountains, enhanced erosion, and seismic activity along the Calabrian Arc and Hellenic Arc, thus potentially resulting in repetitive mass failures. Some of the turbidites observed in the deep basins are thick and prominent on seismic records because of the acoustic transparency of their upper structureless mud layer. Our high-resolution study of the most recent of these megabeds, the homogenite Augias turbidite (HAT), provides key proxies to identify pelagic sediments deposited following the catastrophic causative event. Radiometric dating in an area >150,000 km2 indicates that the different Mediterranean so-called homogenite deposits are in fact synchronous and were deposited during a single basin-wide event within the time window A.D. 364–415. Unlike interpretations that relate this turbidite to different triggering events, including the Santorini caldera collapse, the turbidite can be traced back to a large tsunami sourced from the A.D. 365 Crete megathrust earthquake. Correlation of the single-event HAT over a wide area of the Mediterranean, from the northern Ionian Sea to the Mediterranean Ridge and the anoxic Tyro Basin south of Crete, suggests that the A.D. 365 Crete earthquake and tsunami must have produced devastating effects, including widespread massive sediment remobilization in the eastern Mediterranean Sea.