In 1638, Jacques Dyel du Parquet (1606–1658), nephew of Pierre Belain d'Esnambuc and first governor of Martinique, decided to have Fort Saint Louis built to protect the city against enemy attacks.

Originally named Fort-Royal, the administrative capital of Martinique was over-shadowed by Saint-Pierre, the oldest city in the island, which was renowned for its commercial and cultural vibrancy as "The Paris of the Caribbean".

By the turn of the 20th century, however, Fort-de-France became economically important after the volcanic eruption of Mount Pelée destroyed the town of Saint-Pierre in 1902.

Until 1918, when its commercial growth began, Fort-de-France had an inadequate water supply, was partly surrounded by swamps, and was notorious for yellow fever.

A Sikorsky S-43 (NC15066) on Pan Am Flight 216 arriving from Port of Spain at 10:11 was landed in poor weather conditions due to safety concerns by the crew and subsequently sank within 10 minutes, killing 4 of the 14 occupants.