According to mythology, Uranus and Gaia had many children: the Titans, the Giants, the Cyclopes, and the Hundred-handed. Aware of the fact that one of his sons would dethrone him, Uranus threw them to Tartara, the bottom of the earth. One of his sons was Kalydnos who fell on a piece of land which later emerged to the surface forming a complex of island called "The Islands of Kalydnos". Today, every island has its own name and they all surround the largest, called Kalymnos. The island, with its huge mountains, has two small plains which, if viewed from above, resemble the legs of Kalydnos. According to myth, Kalydnos, once the god of Ades, became a sea god yet no evidence of his worship was ever found.

The first people who inhabited Kalymnos were Kares, Leleges and Pelasgians. The Achaians came to the island after the end of the Trojan War, establishing the town of Argos in the area of Amfipetres. Later, Dorians from Peloponnese settled here, living harmoniously with the locals. After the Greek cities of Asia Minor submitted to the Turks, Kalymnos came under the rule of Artemisia, queen of Alikarnos a true friend of the Persians. The island was a member of the First Athenian Alliance supporting the Athenians in the Peloponnese war, only to come once more under the rule of the Persians and Artemisia B', as the Peace of Andalkides (387 BC) left the islands exposed. Kalymnos was liberated in 333 BC, by Ptolemeus, a General of Alexander the Great. During the Hellenistic Era, Kalymnos submitted to Kos, while, in 44 BC, the island was conquered by the Romans who removed all the art treasures and imposed heavy, unbearable taxation, on the locals. In the Byzantine Era (330-1204 AD), the island suffered pirate raids and the rule of the Persians and the Saracenes while the universal earthquake in 535 AD altered the shape of Kalymnos. In 1306, the island was occupied by the Knights from Rhodes who imposed heavy taxation and work on the locals, without providing any protection from pirate raids. In 1495, the island was attacked by the fierce Turk, Hamza, who occupied the island and raided and massacred the locals, while Kalymnos was destroyed by a new earthquake. Ten years later, the island was attacked by Vayiezit B', but the co-ordinated effort made by both the locals and the Knights scared him away. The Turks occupied the island again in 1523 AD. Kalymnos, like all the Dodecanese islands, participated in the Greek Revolution in 1821, but in London Protocol (1830), did not include the island inside the boundaries of the Greek state. The Turkish Occupation lasted until 1912, when Kalymnos was occupied by Italian troops. In 1943 the island was given over to the Germans until 7 May 1948 when it was united with Greece.