Established in 1884, Mississippi University for Women became the first public college for women in America. Originally known as the Industrial Institute and College, the institution was created by an act of the Mississippi legislature for the dual purposes of providing a liberal arts education and preparing women for employment. The first session began October 22, 1885, with an enrollment of approximately 250 students on a campus formerly occupied by the Columbus Female Institute, a private college founded in 1847.

The name of the institution changed to Mississippi State College for Women in 1920. The name changed again in 1974 to Mississippi University for Women. The university is referred to by alumni and friends as "The W."

In 1982 the Supreme Court of the United States ordered the University to admit a male student to the nursing program.

MUW is located in the Southside district of Columbus, Mississippi, between College Street, Seventh Avenue South, Eleventh Street South, and Fifteenth Street South. In other words, it is in a very dangerous neighborhood, commonly referred to as the "ghetto."

MUW is consistently rated as a "best value" by U.S. News & World Report.

A notable person who attended MUW for one semester, then failed out is author Eudora Welty, for whom the administration building is named.