Louisburg Female Academy opened its doors in 1815, under the direction of Harriet Partridge, making it one of the oldest institutions of higher education for women.

Among the courses offered by the seminary were history, botany, algebra, rhetoric, chemistry, geology, logic, French, Latin, Greek, guitar, and calisthenics.

In August 1857, Louisburg Female College opened its doors under the management of Professor James P. Nelson.

Course offerings included French, Spanish, Italian, piano, guitar, drawing, painting, and needlework.

During the administration of Turner Myrick Jones (1866–1868), former president of Greensboro Female College, enrollment grew to 133 students.

Matthew S. Davis, who had previously served twenty-five years as principal of the male academy, became president of the female college in 1896 and held the office until his death in 1906.

The Reverend Armour David Wilcox, former minister of the Louisburg Methodist Church, served as president of the college from 1931 to 1937.

Student enrollment, faculty size, budget, and physical plant were significantly increased and improved.

The $4.2 million goal of the first phase of the campaign was surpassed, resulting in the construction of the E. Hoover Taft, Jr. Classroom Building.

Through the generosity of the United Methodist Men of the Raleigh District, the Clifton L. Benson Chapel and Religious Life Center was opened in 1986.

During the 1986–87 school year, Louisburg College held a Bicentennial Celebration in recognition of its unique two-hundred-year heritage.