Prior to the Treaty of the Pyrenees in 1659, most of the present department was part of the former Principality of Catalonia, within the Crown of Aragon, therefore part of the Kingdom of Spain, so the majority of it has historically been Catalan-speaking, and it is still referred to as Northern Catalonia.
The modern department was created early during the French Revolution on 9 February 1790 under the name of Roussillon, also the name of the pre-Revolutionary province of Roussillon to which it almost exactly corresponds, although the department also includes Fenouillèdes, a small piece of territory which had formerly been on the southern edge of Languedoc. The name therefore changed on February 26, 1790 to Pyrénées-Orientales.
Invaded by Spain in April 1793, the area was recaptured thirteen months later during the War of the Roussillon.
During the nineteenth century, Pyrénées-Orientales proved one of the most consistently republican departments in France. The intellectual and republican politician François Arago, who, during the early months of the short-lived Second Republic in 1848, was briefly de facto Head of state, came from Estagel in the east of the department.