Built in 1859, it is the only original building of a university chartered by the Republic of Texas still standing. The Old University Building is listed on the National Register of Historic Places.
During the Civil War, the structure served as a Confederate hospital and functioned as headquarters for a federal regiment during reconstruction. The building served the university until deeded to the Nacogdoches Independent School District in 1904 and continued as an educational facility until the 1960s. During that time, its care and use became the charge of the Nacogdoches historical society and later the Federation of Women's Clubs.
The museum depicts 19th century education and a Confederate hospital.