Presque Isle was settled in 1828, and incorporated as a town on April 4, 1859 from Plantations F, G, and H. The town annexed the town of Maysville in 1883, and was incorporated as a city on January 1, 1940. The city was named from the French words meaning almost an island, based on the twists and turns of the Aroostook River and the Presque Isle Stream.
Presque Isle is the hub of Maine Routes 10, 163, 167, 227, and United States Route 1.