Knoxville College is situated on a 17-building, 39-acre campus, located atop a hill overlooking the Mechanicsville neighborhood, just northwest of Knoxville's downtown area.
Along with administration and classroom buildings, the campus includes a performing arts center, a gymnasium, a library, a chapel, and a student center.
The school maintains dormitories for on-campus students, as well as a president's house, and cottages and apartments for faculty.
In 1980, eight buildings on the Knoxville College campus received recognition for having a role in minority education on the National Register of Historic Places as a historic district.
Many of the earliest buildings were constructed using student labor, student-made bricks, and lumber donated by alumni.
The district includes the following buildings: McKee Hall, the oldest building on campus, originally built in 1876, largely rebuilt in 1895 following a fire. The building is named for the Reverend O.S. McKee, who had established the first school for African-American children in Nashville in 1862. This building currently houses administration offices.
In 2016, the preservationist group Knox Heritage placed the Knoxville College Historic District on its "Fragile Fifteen," a list of endangered Knoxville-area historic properties.
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