Nacogdoches University was chartered in 1845 with its first home being the "Red House." In 1858 a permanent brick building was erected on Washington Square. Except for brief periods the university remained in operation until 1895. During the Civil War, the buildings were used for a hospital and quarters for Confederate Soldiers, and during Reconstruction the buildings served as headquarters for a Federal regiment.

When the original charter expired in 1870, management of the university first was under the control of the Catholic church and later of Milam Lodge. From 1887 to 1889 the property was leased to Keachi College and called by that name but after 1889 the name Nacogdoches University was resumed.

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 original brick building has undergone several restorations and is now used as a museum.