Tilos is the homeland of the poetess Irinna, who lived in 350 BC and is considered something between a tenth Muse and a female Homer. The island is linked to the myth of Allia and her son, Tilos. Allia was the sister of Telchines, a kind of satan who enchanted people. According to myth, Tilos arrived at the island to find herbes to heal his ill mother. Afterwards, he came back to the island and became a priest in the temple which he built in honour of Apollo and Neptune. Tilos named the island after himself. In order to interpret the habitation of Tilos by the Cretans, as findings testify, another myth claims that the island was connected with the Minans, since Crete was named. Telchinia, after Tilos's uncles, who "educated" Zeus in Idaion Andron.

In the 5th century BC, Tilos was a member of the Athenian Alliance and had its own coins and economic and cultural growth, which lasted until the end of the 4th century BC. The island was conquered by the Romans in 42 BC, while, during the Byzantine Era, it was a member of the Scheme of Samos. There is no historic information about Tilos for the following centuries, but there is evidence of its habitation. In 1306, Tilos was ruled by the Knights of Rhodes who respected the local authorities, restored the castles and built new ones in order to avoid pirate raids. In 1523, Tilos was occupied by the Turks and their rule lasted until 1912, when the island came under the command of the Italians. In 1943 the island was invaded by German troops and in 1948, Tilos united with Greece, as did all the Dodecanese islands.