About 10,000–13,000 years ago, hunter-gatherer groups took advantage of the area's varied coastal environment, full of food resources. The Tehuelche people, descendants of the first settlers, expanded land use, developing a greater exchange with other, farther away groups. The arrival of the first European settlers triggered major changes in the original populations: the gradual increase of product exchange dependency and loss of territory caused migrations towards the west of the province and the incorporation of the original settlers into rural tasks.

In early 1876, during the presidency of Nicolás Avellaneda and because of increasing tension regarding neighboring Chile's expansion attempts over Argentine Patagonia, Buenos Aires started issuing authorizations for the exploitation of guano in the zone 35 km (22 mi) south of the Santa Cruz River, where 17 years earlier the Argentine commander Luis Piedrabuena had established an outpost. In April the governor of Punta Arenas, Diego Dublé Almeyda, sent the gunboat Magallanes with orders of sinking any Argentine vessels in the area. The French boat Jeanne-Amelie, authorized by Avellaneda's administration, was boarded and its crew imprisoned by the Chilean forces, an incident that worsened the bilateral relationship. Two years later Chile once again seized a vessel in Monte León: this time it was the United States' ship Devonshire, and the action put both countries at the verge of war.

Francisco P. Moreno, naturalist and creator of the Argentine National Park System, and the paleontologist Carlos Ameghino explored the area in the late 19th century. The Italian missionary Alberto María De Agostini also visited it in the early 20th century.

 Park logo with Magellanic penguin

The Estancia Monte León belonged to the Southern Patagonia Sheep Farming Company Limited, which exploited it as a sheep farm. It was sold in 1920 to the Braun family, who continued this business until 2006. The extraction of guano was profitable until 1930.

In 1996 Monte León was proposed to be included in the National Park System of Argentina. Francisco Erize, former director of the Argentine National Parks Administration, recommended the project to Douglas Tompkins, a billionaire businessman, environmentalist, and founder of Tompkins Conservation, a conservationist NGO.

In 2000, through the NGO Conservación Patagónica, founded and directed by Kristine Tompkins, the farm land was acquired and transferred by land trust to Fundación Vida Silvestre Argentina, demanding it to be donated to the National Parks National Administration, a process finished in 2002. Finally, on 20 October 2004 the law creating the new national park was sanctioned by Congress, making Monte León the first continental marine park of Argentina.