Old Main was constructed between 1873 and 1875 as part of a land grant. Originally known as University Hall, it is the oldest building on the University campus and one of the oldest buildings in the state. The firm of Mayes and Oliver constructed the building of local materials, under the watchful eye of Judge Lafayette Gregg of Fayetteville. Cost of the 100,000 square foot building was $130,000. The building plans for Old Main were copies from architect John Mills Van Osdel's University Hall at the University of Illinois. That building no longer exists. Many of the building materials used in Old Main came from surrounding areas: lumber came by oxen-pulled wagonloads from the Peter Van Winkle Sawmill near historic War Eagle Mill in Benton County; the red exterior bricks were made from clay dug nearby and fired in kilns built west of Old Main; the brown sandstone used for the foundation and basement was also quarried near the building site.

It was used until 1981 when it was closed for safety reasons after having fallen into disrepair. Restoration work began in the late summer of 1989 and Old Main was extensively renovated. The renovation proceeded ahead of schedule, and it was finished during the 1991 Spring semester. Its rededication in the Fall of 1991 was a highlight in the history of the University of Arkansas. In its long history, Old Main has housed many departments and served many administrative functions. It currently quarters the offices of the Fulbright College of Arts and Sciences, its honors program and five academic departments as well as classrooms and meeting spaces.