Ammianus Marcellinus, a fourth‐century writer, reported that after an earthquake, on 21 July 365, the sea retreated and then flooded numerous coasts, among them Alexandria (Egypt) and Methoni (southwest Greece). Several other ancient authors seem to mention this event as a “universal earthquake.” The inferred tsunami is usually assigned to reactivation of a fault in the Hellenic (Aegean) Arc, derived from an up to 9 m seismic uplift of Crete. Modeling of this uplift revealed an 8.5+ magnitude earthquake and a tsunami that affected most of the Eastern Mediterranean. For Alexandria, a flooding wave arrival is predicted, and marginal impacts are not excluded because of the topography of the ancient town. On the other hand, ancient sources lead to contradictory results, from no damage to devastation, but new historical evidence indicates that many of the historical reports of the critical period are biased by religious and political ideas, and the Ammianus description was questioned. Hence, for Alexandria there exist three scenarios: major destruction, marginal damage, and no damage by the 365 tsunami. To shed light to this debate (1) ancient sources were analyzed in view of new evidence for their significance, (2) possible impacts of a tsunami in the town’s infrastructure were discussed, and (3) possible impacts of a major destruction were investigated in the framework of the well‐known ecclesiastical and civil history of Alexandria. The main conclusions of this study are that (1) no significant tsunami destruction is likely for Alexandria, in agreement with sedimentary evidence, and no major tsunami runup for Methoni; (2) a major earthquake in 365 is likely offshore Crete; and (3) it is inferred that Ammianus brings together two tsunamis, a local slump offshore that produced water retreat and then flooding and local denudation in the eastern Nile Delta, and a second tsunami generated by a fault offshore Crete or in the Ionian and the Adriatic Sea.