[3] The building was constructed from 1858 and 1871 and "represents" the college's "pivotal historical role as the headquarters of Alexander Campbell (1788–1866), a principal founder of the Christian Church (Disciples of Christ).

"[4] It is "intimately linked to the Scots-Irish ethnic settlement of the American frontier," and "Old Main is one of the country's earliest intact large-scale examples of collegiate Gothic architecture.

[5] John F. Kennedy spoke at its Commencement Hall in 1960 during his presidential primary campaign that won West Virginia.

[2][6] The Old Main building includes Commencement Hall, used for concerts, convocations, lectures, dramatic presentations, special functions, dinners, and other gatherings; Kirkpatrick Hall of Life Sciences, devoted to biology, microbiology, and botany laboratories, a greenhouse, faculty offices, a student library and conference room, a psychology computer laboratory, an experimental psychology laboratory, an animal research laboratory, a cold room for experiments, classrooms relating to the life sciences, a classroom for environmental science, and a student psychology lounge; the Media Center, used for administration, use, storing and dispensing of media equipment; the Academic Parlour, used for lectures, receptions, and special gatherings; the Trustee Board Room, used for board of trustees meetings; Trustee Hall of Fame Room, used for receptions; Office of the Vice President and Dean of Faculty, a suite of rooms to the left of the main entrance; Office of the President, a suite of rooms to the right of the main entrance; seminar rooms; webmaster information technology center; and classrooms, many of which are dedicated to professors, alumni, trustees, administrators.

[7] Society Hall was ready for use at the opening of the 1858 session, and by the close of the year 1859, 150 feet of frontage of the New Edifice had been completed.

[7] It was used as classroom and laboratory space for biology, chemistry, physics, and agricultural science and contained the offices of the president and dean.

[7] An additional front entrance was added as a passageway between Oglebay Hall and the one-story connecting section adjoining it to the south.

[7] Thayer and Johnson were hired to be the architects on February 2, 1922, and the windows of Commencement Hall were remodeled in Gothic style.