[4] The Cherokee Council chose to rebuild the school on a 40-acre (160,000 m2) site north of Tahlequah, Oklahoma near Hendricks Spring.

[5]The Female Seminary was owned and operated by the Cherokee Nation until March 6, 1909, after Oklahoma had been admitted as a state as in 1907, and tribal land claims were extinguished.

Female seminaries were a larger cultural movement across the United States in the mid-nineteenth century, by which time they had taken over the role played traditionally by the boarding school, which had offered a more family-like atmosphere.

[7] The staff included teachers and a medical superintendent as Cherokee social progress placed an increasing emphasis on providing quality healthcare alongside education.

[8] The Cherokee Female Seminary in Tahlequah was designed after Mount Holyoke in Massachusetts and its first two teachers were alumni of the school, Ellen Whitmore and Sarah Worcester.

[5] Miss Florence Wilson served as the principal of the Cherokee Female Seminary at both its original and rebuilt site from 1875 to 1901.

According to the Cherokee Advocate newspaper, up to three thousand people attended the reopening celebrations in a precession that totaled a mile long.

It was built in 1889 by St. Louis architect Charles E. Illsley, who designed it in the Romanesque Revival style, complete with fortress-like turrets flanking the main entrance and a clock tower that resembles a church steeple and rises two stories above the rest of the building.

At the main entrance of the building are three murals painted in the 1930s as a WPA project by Stephen Mopope, Jack Hokeah (both Kiowa), and Albin Jake (Pawnee).

[16] The first class to graduate from the Cherokee Female Seminary had two students, Tennie Steele Fuller and Belle Cobb.