Piscataquis County was incorporated on 23 March 1838, taken from the western part of Penobscot County and the eastern part of Somerset County. It is located at the geographic center of Maine. Originally it extended north to the Canadian border, but in 1844 its northern portion was annexed by Aroostook County. In land area, Piscataquis is one of the largest U.S. counties east of the Mississippi River. It is also one of two counties in the Northeast (and seven counties east of the Mississippi River) that meets Frederick Jackson Turner's requirements for "frontier" country - that is, having fewer than six inhabitants per square mile, the other being Hamilton County, New York.
Piscataquis is an Abenaki word meaning "branch of the river" or "at the river branch."
Baxter State Park, a large wilderness preserve, is located in Piscataquis County.