In January 1846, the board of trustees selected architect William Nichols to oversee construction of the university and approved his proposed design for the university's central building,[1] which he based the design on an Ionic Temple on the Illysis near Athens.

[2] Daniel Grayson of nearby Panola County was chosen by the Board to manage construction of the building as contractor.

He had served in a similar role overseeing construction of Lafayette County's first brick courthouse, completed in Oxford in 1840.

for the building's construction was provided by enslaved African American workers, whose owners received payments for their work.

[8] In 1859, Chancellor Frederick Augustus Porter Barnard built a 36-foot (11 m) addition to the Lyceum, extending from the rear (west side) of the building.

The addition of the wings was controversial, with the school magazine writing that it compromised the Lyceum's classical design.

[10] By 1916, the University of Mississippi had an undershortage of dormitories, resulting in students being housed in the basement of the Lyceum.

Although Kansas troops destroyed much of the medical equipment, a lone remaining professor persuaded Grant against burning the campus.