Affiliated with the Methodist Episcopal Church, South, it opened in 1859 and closed in 1927.
As a result of the war, the college sank deep into debt for a decade, until it was purchased by Moses U. Payne of Rocheport in 1869.
Howard-Payne was closely associated with several other Missouri junior colleges for women.
In 1918, it was one of the eight charter colleges of the Phi Theta Kappa honor society.
In 1923, Howard-Payne received formal accreditation from the Higher Learning Commission and also participated in the HLC's Program to Evaluate and Advance Quality (PEAQ).