Scio College originated as the Rural Seminary in 1857, in Harlem Springs, Ohio. In 1867, the institution relocated to New Market, Ohio, where it became known as New Market College. In 1875, New Market College became "The One Study University." The institution was so named because students focused on one area of study, forsaking courses outside of their respective majors. This view of higher education quickly gave way to the more traditional view of providing students with a well-rounded education, and in 1877 or 1878, the institution became Scio College.
Scio College began principally as a college to educate future ministers of the Methodist Episcopal Church. By the first decade of the 1900s, the institution suffered from low enrollment and a shortage of funds. In 1908, Scio College's College of Pharmacy ceased to exist when its students transferred to the Pittsburgh College of Pharmacy. In 1911, Scio College merged with Mount Union College, in Alliance, Ohio, bringing Scio's history to a conclusion.