Puerto San Julián was given its name by the leader of a Spanish expedition, the Portuguese navigator Ferdinand Magellan, who arrived there on 31 March 1520 and stopped for the winter with his crew in the harbour, staying for five months.

The term is most likely derived from an actual character name, "Patagón", a savage creature confronted by Primaleón of Greece, the hero in the Spanish chivalry novel by Francisco Vázquez, published in 1512, much in fashion at the time, and a favourite reading of Magellan.

The settlement of Floridablanca, a short lived Spanish colony of approximately 150 people,[5] was founded not far from San Julián in 1780 by King Charles III.

While HMS Beagle carried out its hydrographic survey, Darwin explored the local geology in cliffs near the harbour and found fossils of pieces of spine and a hind leg of "some large animal, I fancy a Mastodon".

During the late 19th and early 20th centuries, San Julián and the surrounding countryside (or "camp" as it was known in the argot of the day) was an important sheep-raising region, and the "Swift" company installed a frigorifico, or freezer plant complex, along the coast to the north of the city itself.

During the 1982 Falklands War (Spanish: Guerra de las Malvinas/Guerra del Atlántico Sur), as San Julian is one of the nearest point to the islands, the city airfield was used by the Argentine Air Force.