In 1520, Magallanes discovered the estuary that he called Río de los Trabajos.
In 1578, the English Francis Drake travelled around the area with the intention of sacking the Spanish colonies. In 1586, Cavendish gave the place the present name in homage to his ship, called Desiré.
On 23rd March 1780 arrived to San Julián a squadron commanded by Antonio de Viedma. Since the area was not good for anchoring, he tried to continue to Santa Cruz, but the winds took him to the place today occupied by Puerto Deseado, where he had to spend the winter.
There they built the first houses, organized the first vegetable gardens, and cultivated wheat for the first time in Patagonia.
Short time after, there was an epidemic of scurvy that caused the death of the first Spanish Settlers.
Antonio de Córdoba presented, requested by the Spanish Crown, a report about the possibility of setting colonies in Patagonia, in which he described this part of Patagonia as " the most despicable and poorest part of the world", what gives an idea of the struggle meant by these colonizing expeditions.
Nevertheless, in July 1789, left from Cadiz an expedition commanded by Alejandro Malasapina to explore, recognize and write a confidential report for the Crown about the situation in the domains.
The expedition went through Buenos Aires and stopped in Deseado, where they made friendly contact with Tehuelche aborigines.
A secons attempt of colonization was performrd between 1790 and 1807 in Puerto Deseado with the settlement of a fishing company for the capture, salting of leather, and the elaboration of oil. Years passed and the fishing company continued its activity until an English frigate caused important destructions in Puerto Deseado parallel to the English invasions to Buenos Aires, what caused a dismantling and a ceasing of the factory's activities. In October 1807, colonists were transported to Patagones, and the fishing company was abandoned.
In 1834 Charles Darwin and Fitz Roy travelled around Patagonia and made an incursion to river Santa Cruz.
On 1st December 1878, the government, by means of the Navy (Fuerza Naval Militar), took possession of the territory in the site known as Cañadón de los Misioneros, and on 16th October 1884 passed law 1532 to create the government of Santa Cruz, being appointed governor the explorer Captain Carlos María Moyano.
In 1880 the government created a colony. Finally on 15th July 1884 Captain Oneto disembarked with a group of colonists to settle in the recently created colony, thus originating Puerto Deseado.
In 1881 a delegation of Prefectura Naval Argentina settled in the southern margin of the estuary.
In 1887, Lista was appointed to replace Moyano. He travelled to Puerto Deseado on board of the Magellan to take charge, and while entering the bay, the ship crashed against a rock and shipwrecked. Three people from the crew died, and all the shipment was lost. In the port, a small colony hardly survived. While Lista went on horesback to Puerto San Julián, a group of colonists prepared a small ship with supplies and went off to Patagones to ask for help in Buenos Aires.
Lista informed about the precarious conditions and struggles of the colony, advising to dismantle it. Notwithstanding the colonists decided to stay, and after twelve years of bearing all types of shortage, they were recognized by the government, which proclaimed the foundation of the town of Puerto Deseado in 1899.