The largest of a series of earthquakes struck the island of Rhodes, causing an estimated 30,000 casualties.

The 1481 Rhodes earthquake occurred at 3:00 in the morning on 3 May. It triggered a small tsunami, which caused local flooding. There were an estimated 30,000 fatalities. It was the largest of a series of earthquakes that affected Rhodes, starting on 15 March 1481, continuing until January 1482.

Rhodes is the largest of the Dodecanese islands of Greece and is their historical capital; it is the ninth largest island in the Mediterranean Sea. Administratively, the island forms a separate municipality within the Rhodes regional unit, which is part of the South Aegean administrative region. The principal town of the island and seat of the municipality is the city of Rhodes, which had 50,636 inhabitants in 2011. In 2022, the island had a population of 125,113 people. It is located northeast of Crete and southeast of Athens. Rhodes has several nicknames, such as "Island of the Sun" due to its patron sun god Helios, "The Pearl Island", and "The Island of the Knights", named after the Knights of Saint John of Jerusalem, who ruled the island from 1310 to 1522.