The eastern Mediterranean Sea is a subduction zone between the African plate and the Eurasian plate that has high seismicity. The tsunami of July 21, 365 AD was one of the most severe in the region, and its impact was estimated to have extended to the islands around the Aegean Sea, Cyprus, southern Calabria, Sicily, Malta, and Lampedusa. However, an analysis of tsunami waves reaching Lampedusa Island has not been conducted. Therefore, this study will present the run-up height and arrival time of tsunami waves near the Lampedusa coast. The methods applied are linear and non-linear shallow water equations by inputting the rupture parameters of the 365 AD earthquake. We used Delft Dashboard and Delft3D software to simulate tsunami wave propagation offshore. The simulation results indicate that an earthquake with a magnitude of approximately Mw 8.5 triggered tsunami waves with a maximum run-up height of 2.02 m in nearshore Lampedusa. The travel time for the maximum run-up height was 3.5 hours after the generation of the first tsunami wave in the western Hellenic Arc, Greece. We infer that seawater most likely inundated the coast of Lampedusa during the tsunami earthquake in 365 AD.