While the beauty of the beaches on Cayo Coco is now world famous, pre-1990 the island was little more than a mosquito-infested mangrove swamp. Early visitors included Diego Velázquez, who named the islands in honor of then King of Spain, Ferdinand II, and later French corsair Jacques de Sores, fresh from successful raids on Havana and Puerto Príncipe. Between 1927 and 1955 a community of 600 people scraped a living by producing charcoal for use as domestic fuel on the island but, with the rise of electrical power after the Revolution, this too died.

Fishers have always visited the keys, the most famous of them Ernest Hemingway, who loved to fish and hunt off Cayo Coco and its smaller neighbors from the 1930s onward on his beloved boat, Pilar. Hemingway also, allegedly, tracked German U-boats in these waters in the 1940s, his own personal contribution to the war effort.