Except for brief periods the university remained in operation until 1895. During theCivil War the buildings were used for a hospital and quarters for Confederate soldiers, and duringReconstruction the buildings served as headquarters for a federal regiment.

When the original charter expired in 1870, the Catholic Church took over the management of the university until the charter was renewed on February 11, 1873. In 1875 Milam Lodge Number 2 assumed control. In 1887 the property was leased to Keachi College. In 1889 the name Keachi College was dropped and that of Nacogdoches University was resumed.

When the second charter of the university expired in 1895, it was apparent that instruction could no longer be maintained on the university level, and in 1904 the property was deeded to the Nacogdoches Independent School District. The main building was used by the Nacogdoches public schools until the 1930s. After years of disrepair, it was restored in the 1960s and converted into a museum featuring early Texas furniture, vintage clothing, manuscripts, deeds, silver, and other relics. In 1962 the structure became a Registered Texas Historical Landmark; in 1971 it was added to the National Register of Historic Places.