Mayaguana was inhabited by Lucayans prior to the arrival of the Spanish following 1492. After the last of the Lucayans were carried off to Hispaniola by the Spanish early in the 16th century, the island remained uninhabited until 1812, when people began to migrate from the Turks and Caicos Islands, which are located about 100 km southeast.
The Brazilian historian Francisco Adolfo de Varnhagen suggested in 1824 that Mayaguana is Guanahani, the first island visited by Christopher Columbus at his discovery of the Americas. His theory has found little support. Mayaguana apparently was the Lucayan name for the island.Julian Granberry and Gary S. Vescelius. (2004) Languages of the Pre-Columbian Antilles. The University of Alabama Press. ISBN 0-8173-5123-X p. 83
The first steamship to circumnavigate the globe, the Royal Navy sloop HMS Driver, was wrecked on Mayaguana on 3 August 1861, 14 years after the completion of her epic voyage in 1847.
During NASA's Project Mercury and the Apollo program, the United States space program had a missile tracking station on what is now Mayaguana Airport. The station was used to help keep astronauts on course.
The Bahamian government has recently approved working with American investors MMC to turn Mayaguana into a "free trade zone," complete with tourism development of approximately 14% of the island. Actually, this is 14% of the total landmass but essentially most of the coastal region. The proposal was met with moderate resistance by Mayaguanians, who look forward to economic expansion but are unsure of what change is to come. This development is still in a planning phase and is trying to maintain the nature of the island as a quiet eco-tourist destination while still creating sustainable economic growth.