Some time in the Greek Dark Ages (1150-800 BCE) the Achaeans arrived, after the decline of Minoan Crete. By the 11th century BCE the Dorians invaded Kos and expelled the Achaeans. In the Archaic Period (800-500 BCE) the islands of Kos, Nisyros, Karpathos, and Kalymnos played an important part in the Trojan War according to The Odyssey. After the fall of Troy, local Greek mythology presents: "Podarios, son of the god Asklepios, the Doctor from Thessaly, settled on the island after a shipwreck. From this time, the family of the Asklepidai lived on the island (Hippocrates was introduced as the 18th descendant).

In the 7th century BCE, Kos joined a federation with six other cities in Asia Minor, Rhodes, Kalymnos and Nisyros. Later during the Classical Period (500-336 BCE), the island of Kos was subdued by the Persians, as were the other cities of Asia Minor. In 479 BCE the island was represented at the battle of Salamina (where Xerxes was defeated). During the Peloponnesian war (431-404 B.C.E.) Kos allied with Athens. For this the island paid a high tribute when the Spartan Commander Astochos invaded the island in 411 BCE. In 394, after a brief treaty with Sparta, the Koans once again allied with Athens. Under the influence of Athens democracy was introduced. Life on Kos was stable and the island enjoyed prosperity until the invasion of King Mausolos of Halikarnasos in 358. The island recovered under Alexander and the Diadoche. In 334 BCE the island allied with Macedonian and Alexander the Great. The ports became places of supply for the advancing Greek armies.

During the Roman Period Kos became a part of the Eastern colony of the Roman Empire and was granted special privileges (from 82 BCE). Some of these were stripped away during the reign of Augustus and cause a decline that was compounded by a terrible earthquake in 27 BCE. The island recovered again, in part due to its important reputation as a healing center. In the Book of Acts, the island was an overnight stop during part of Paul's journey to Jerusalem. Paul came from Miletus, and sailed to Coos, Rhodes and Patara (Acts 21:1).

By the Byzantine Period (300-1000 CE) Kos flourished as part of the Byzantine Empire. Close to Asia Minor, the island was continuously attacked by both pirates and Turks. By the Crusader Period, (1204 CE) the island was occupied by the Venetians. The Ottoman Rule (1450-1830) began in 1457 CE, when a powerful Turkish army looted the island. Turks again subdued the island under Sultan Sulieman, but the Koans continued with a resistance movement. On May 5th, 1912 Italian troops invaded the island and expelled the Turks. In 1934 an earthquake destroyed 80% of the housing and monumental architecture of the island, but most was later restored. Occupation continued under the Germans in 1943. The 18 months of German occupation brought inhumane suffering to the Koans. In 1945 the island came under British control and was rebuilt. Finally, on March 7th, 1948 it became part of modern Greece.