Incorporated in 1838, Piscataquis County once extended north to the Canadian border, but its northern portion was annexed by Aroostook County in 1844. Still, in land area, Piscataquis is one of the largest counties east of the Mississippi River, with 3,780 square miles. The county is landlocked, geographically located in the center of Maine, with Somerset County on the west and Penobscot County on the east.
The name "Piscataquis" is an Abenaki word meaning "branch of the river," or "rapid waters."