French Guiana was originally inhabited by a number of indigenous American people. It was settled by the French during the 18th century. According to Bill Marshall, "The first French effort to colonize Guiana, in 1763, failed utterly when tropical diseases and climate killed all but 2,000 of the initial 12,000 settlers. During its existence, France transported approximately 56,000 prisoners to Devil's Island. Fewer than 10 percent survived their sentence. The coast of Guiana was sighted by Columbus in 1498 and explored by Amerigo Vespucci in 1499. The French established the first successful trading stations and settlements, and placed the area under direct control of the French Crown in 1674. Portuguese and British forces occupied French Guiana for five years during the Napoleonic Wars. Devil's Island, the notorious penal colony in French Guiana where Capt. Alfred Dreyfus was imprisoned, was established in 1852 and finally closed in 1947. Therefore its infamous known as Île du Diable (Devil's Island), the site of penal settlements from 1852 until 1951.  When France adopted a new constitution in 1946, French Guiana voted to remain within the French Union as an Overseas Department.

In 1809, a Portuguese-British naval squadron took French Guiana for the Portuguese Empire. With the signing of the Treaty of Paris in 1814 the region was handed back to the French, though a Portuguese presence remained until 1817.

A border dispute with Brazil arose in the late 19th century over a vast area of jungle, leading to the short-lived pro-French independent state of Counani in the disputed territory and some fighting between settlers, before the dispute was resolved largely in favour of Brazil by the arbitration of the Swiss government. Counani [Republic of Independent Guyana (French: La République de la Guyane indépendante)] was created in the area that was disputed by France (as part of French Guyana) and Brazil in the late nineteenth century. The state was founded by French settlers and existed from 1886 to 1891. The territory of the former state of Counani is now located in the Brazilian state of Amapá. Some pattern coins of 10 centimes (bronze), 20 centimes (Copper-Nickel-Zinc) and 5 Francs (.900 silver and White metal), all dated 1887 are well known.

In 1946, French Guiana became an overseas department of France. The 1970s saw the settlement of Hmong refugees from Laos.

In 1964 the French president, Charles de Gaulle, decided to construct a space-travel base in French Guiana. This would replace the existing Sahara base in Algeria and stimulate economic growth in French Guiana. A large part of the department's economy derives from the presence of the near-equatorial Guiana Space Centre, the European Space Agency's primary launch site. The department is particularly suitable for the purpose both because it is near to the equator and because of the extensive access to a large ocean. The Guiana Space Centre a short distance along the coast from Kourou has grown considerably since the initial launches of the “Véronique” rockets, and has brought commercial success to the European space industry with launchers such as the Ariane 4 and Ariane 5.

A movement for increased autonomy from France gained some momentum in the 1970s and 1980s, but has since abated.

In the late 18th century, a series of 2 sous coins was struck for the colony as Colony of Cayenne, mainly dated 1789. It is probable that contemporary imitations of these issues, many emanating from Birmingham, England, outnumber the originals. These, both genuine and bogus, host coins for many West Indies counterstamps, Livre = 20 Sols (Sous) = 80 Liards. Notable coin of Colony of Cayenne are: 2 Sous 1789A and 2 Sous 1816A billion. French Francs = 100 centimes were used till 31st Dec 2001.

In 1794, as an Overseas Department, Guiana used the coins of France, Franc = 100 centimes. However, the Franc used in the former colony was always distinct in value from that of the homeland as well as that used in the islands of the French West Indies. Later on 01st January 2002, Euro was introduced.