Pickaway County was established by an Act of the General Assembly of Ohio at the (then) state capital of Chillicothe, on January 12, 1810 with the Act to become effective on March 1, 1810. The name Pickaway is derived from the words Piqua, Pickaweeke, Peckawee or some other variation of the name of a sept of Shawnee that had settled in the Pickaway Plains area of the county.

Circleville is the county seat and only city within Pickaway County. It takes its name from an ancient earthwork, a circle with a diameter of about 1140 feet, and an adjacent square measuring over 900 feet on each side where the early town was built.