The first European settlers were British Loyalists who reached the area in 1819 hoping to obtain land for lumber. Border disputes between the United States and the United Kingdom over the area, however, made it impossible for pioneers to gain title to the land. In response, the government of the neighboring British colony of New Brunswick (now a Canadian province) gave out patents for pioneers to live on the land but not claim ownership or sell it. By 1825, surveyors traveling along the Aroostook River noted that twenty families lived along it and noted that while agriculture was present, all of the families employed most of their time towards wood production.<ref name="History of Presque Isle">Template:Cite web</ref>
The boundary dispute slowed development in the area, but the government of Massachusetts, which governed the territory at the time, saw the territory as theirs and encouraged the development of settlements in northern Maine by offering land grants and mill privileges in the 1820s. The first American to settle in the area was Dennis Fairbanks in 1828 who gained ownership over the land under the provisions set up by Massachusetts and later Maine, which gained statehood in 1820.<ref name="History of Presque Isle" />
Originally known as Fairbanks for its founder Dennis Fairbanks, Presque Isle was settled in 1828 on land that was unknown to be part of British North America (Canada) or the United States. The Aroostook War broke out in 1838 because of boundary disputes between the two countries, which were resolved in 1842 by the Webster-Ashburton Treaty. The township was incorporated from Plantations F, G and H on April 4, 1859, as Presque Isle, derived from the French term for peninsula (presqu'île), as the courses of the Aroostook River and Presque Isle Stream form a peninsula. In 1864, Fairmount Cemetery was established in the south of Presque Isle to accommodate Union soldiers returning from the Civil War. In 1883, the town of Maysville was annexed.
On January 1, 1940, Presque Isle was incorporated as a city.
During the last 30 years of the 19th century, agriculture became important, and the entire county became noted for its production of potatoes. On October 9, 1851, the first Northern Maine Fair exhibition opened. A starch factory was opened in 1874, providing a ready market for local potatoes.<ref name="Sebold">Template:Cite web</ref> In 1914 the Aroostook Farm was purchased as a Maine Agricultural Experiment Station.<ref name="Smith 1980">Template:Cite book</ref>
A small airport was established in 1931. It was expanded within the decade and later assumed major military importance. The Presque Isle Air Force Base, in operation between 1941 and 1961, was a major departure point for U.S. fighter planes during World War II and the Korean War due to its relative proximity to Europe. When the base was sold, a piece of it became the Northern Maine Regional Airport. In June 2018, the Northern Maine Regional Airport was renamed Presque Isle International Airport.<ref>Template:Cite web</ref>
On 4 June 2024, the US Dept. of Transportation awarded Jet Blue its first ever essential air service contract to replace United Airlines at Presque Isle. The service will be less frequent, but offer more capacity to Boston Logan, than the previous service offered to Newark Liberty International.
In 1903, the Aroostook State Normal School began offering a two-year teacher preparation program. In 1968, it was renamed the University of Maine at Presque Isle. Northern Maine Technical College was established in 1961, now Northern Maine Community College.<ref name="NMCC">Template:Cite web</ref> The first students entered the college in 1963. Today it serves about 2000 students.<ref name=NMCC />
The first Presque Isle Hospital was established on April 8, 1912.<ref name="Hospital 1984">Template:Cite book</ref> Four physicians were affiliated with the hospital, whose dual aims were to serve the community and to provide a training school for nurses.<ref name="Hospital 1984" /> The building was a white-frame structure, enlarged from a home under construction. The need and demand for the hospital increased so rapidly that in 1921 a new three-story brick hospital was dedicated.<ref name="Hospital 1984" /> This hospital was in operation for nearly four decades, when it, too, proved inadequate. A major fundraising campaign was launched in the late 1950s. After a large donation was given by Mr. and Mrs. W. H. Wildes, the daughter of the late Senator Arthur Gould, the Arthur R. Gould Memorial Hospital was constructed and opened in 1960.<ref name="Hospital 1984" /> The hospital has expanded and been modernized in recent years, and in 1981 became part of The Aroostook Medical Center.<ref name="Hospital 1984" />
On August 11, 1978, the Double Eagle II was launched from a Presque Isle field carrying three passengers. It made the first successful transatlanticballoon crossing. In honor of the Double Eagle II, the city holds an annual celebration called The Crown of Maine Balloon Festival. The popular event includes balloon rides, plane tours, amateur photo contests and children's fair rides. Sponsored by the Chamber of Commerce and other local organizations, it is held in late August. The field from which the Double Eagle II lifted off now features a commemorative model balloon.<ref>Double Eagle II – Maine Office of TourismTemplate:Webarchive</ref>
There were 4,201 households, of which 25.7% had children under the age of 18 living with them, 41.1% were married couples living together, 12.1% had a female householder with no husband present, 4.2% had a male householder with no wife present, and 42.6% were non-families. 34.2% of all households were made up of individuals, and 13.3% had someone living alone who was 65 years of age or older. The average household size was 2.19 and the average family size was 2.78.
The median age in the city was 40.2 years. 19.6% of residents were under the age of 18; 12.4% were between the ages of 18 and 24; 24.1% were from 25 to 44; 27.8% were from 45 to 64; and 16.2% were 65 years of age or older. The gender makeup of the city was 48.2% male and 51.8% female.
There were 3,963 households, out of which 28.1% had children under the age of 18 living with them, 47.8% were married couples living together, 11.0% had a female householder with no husband present, and 37.8% were non-families. 31.0% of all households were made up of individuals, and 13.7% had someone living alone who was 65 years of age or older. The average household size was 2.25 and the average family size was 2.82.
In the city, 21.6% of the population was under the age of 18, 13.1% was from 18 to 24, 27.0% from 25 to 44, 22.4% from 45 to 64, and 15.9% was 65 years of age or older. The median age was 37 years. For every 100 females, there were 91.3 males. For every 100 females age 18 and over, there were 88.2 males.
The median income for a household in the city was $29,325, and the median income for a family was $37,090. Males had a median income of $27,510 versus $19,785 for females. The per capita income for the city was $15,712. About 9.2% of families and 14.5% of the population were below the poverty line, including 16.1% of those under age 18 and 15.2% of those age 65 or over.
Due to being Aroostook County's largest city, Presque Isle is the retail center for a large number of both American and Canadian towns. The Aroostook Centre Mall became a major shopping center for residents during the 1990s. Agriculture remains a top industry of Presque Isle and the surrounding area, with potatoes being the top crop. During the winter months many local businesses rely on the snowmobiling industry as there is a highly regarded trail system connecting far away towns and cities with Presque Isle. Presque Isle is also home to a significant industrial park near the Presque Isle International Airport.
The unemployment rate in Presque Isle is typically somewhat higher than the average across Maine.
Presque Isle is home to one of the smallest TV markets as defined by Nielsen market research. It consists of WAGM-TV channel 8 (a CBS/Fox/CW+ affiliate), sister station WWPI-LD channel 16 (an NBC affiliate which launched on January 7, 2020), and WMEM-TV channel 10 (affiliated with the Maine Public Broadcasting Network ("Maine Public") and PBS). While not part of the Presque Isle TV market, WVII-TV, the ABC affiliate out of Bangor, Maine, airs in Presque Isle, as does NBC affiliate WLBZ.
There are no daily newspapers in Aroostook County. The Presque Isle Star-Herald is published Wednesdays, one of several weekly newspapers published in Aroostook County. Others include Caribou's Aroostook Republican, Madawaska's St. John Valley Times, The Fort Fairfield Journal and Houlton's Pioneer Times. The Bangor Daily News has an Aroostook County edition.