In 1520 the estuary provided shelter to Hernando de Magallanes after a crippling storm waylaid his fleet; he dubbed the area ‘Río de los Trabajos’ (River of Labors).

In 1586 English privateer Thomas Cavendish explored the estuary and named it after his ship Desire, its name today. The port attracted fleets from around the world for whaling and seal hunting, compelling the Spanish crown to send a squadron of colonists under the command of Antonio de Viedma. After a harsh winter, more than 30 of them died of scurvy. Those who survived moved inland to form the short-lived colony of Floridablanca. In 1834 Darwin surveyed the estuary, as did Perito Moreno in 1876.