In Homer's Iliad, a contingent from Kos fought for the Greeks in the Trojan War.

In the Roman mythology, the island was visited by Hercules.The island is originally colonized by the Carians.

The Dorians invade it in the 11th century BCE, establishing a Dorian colony with a large contingent of settlers from Epidaurus, whose Asclepius cult makes their new home famous for its sanatoria.

The other chief sources of the island's wealth lie in its wines and, in later days, in its silk manufacture.

Its early history–as part of the religious-political amphictyony that includes Lindos, Kamiros, Ialysos, Cnidus and Halicarnassus, the Dorian Hexapolis (Greek for six cities),–is obscure.

At the end of the 6th century, Kos falls under Achaemenid domination but rebels after the Greek victory at Cape Mykale in 479.

During the Greco-Persian Wars, when it twice expels the Persians, it is ruled by tyrants, but as a rule it seems to have been under oligarchic government.

In the 5th century, it joins the Delian League, and, after the revolt of Rhodes, it serves as the chief Athenian station in the southeastern Aegean (411–407).

In 366 BCE, a democracy is instituted.

After helping to weaken Athenian power, in the Social War (357-355 BCE), it falls for a few years to the king Mausolus of Caria.

In 366 BCE, the capital is transferred from Astypalaia to the newly built town of Kos, laid out in a Hippodamian grid.Proximity to the east gves the island first access to imported silk thread.

Aristotle (384 BCE-322 BCE) mentions silk weaving conducted by the women of the island Silk production of garments is conducted in large factories by enslaved women.