Located at the southern terminus of U.S. Highway 1.

1733 Spanish shipwreck chart shows Cayos de Guezo. Antonio de Arredondo chart (1742) shows Cayo Gueso. Juan de Liguera chart (1742) shows Cayo de Huesos. Father Alaña's chart (1743) shows Cayo de Guesos. Thomas Jefferys' chart (1769) shows West Kay. O'Carol Plano (1770) shows Cayo de Muessos. DeBrahm Chart (1772) shows Hueso. The Gauld-Faden chart (1790) shows "Cayo Huesso commonly called Kay West." Blunt chart (1846) shows Thompson's Island, Port Rogers, or Key West.

Popular legend has always held that Key West received the name Cayo Huesso (Sp. Bone Key) at some point in the late 18th century. However, a Spanish Document from the State Archive In North Carolina dated June 14, 1681 refers to "the enemy gathering at Cayo de Guesas" in order to Invade Havana. In the nineteenth century, especially after 1821, when Florida became a U.S. territory, Key West developed into the major center of population and commerce of South Florida.