Missouri State University was founded in Springfield in 1905 as the Fourth District Normal School. During its early years, the institution's primary purpose was the preparation of teachers for the public school systems in the southwest region of Missouri. The first name change came in 1919 when the school became Southwest Missouri State Teachers College, reflecting its regional mission. 

By the mid-1940s, the University had expanded its instructional program beyond teacher education to include the liberal arts and sciences; and as a consequence, the Missouri legislature, in 1945, authorized an official change in the institution's name to Southwest Missouri State College. 

By 1972, as additional programs were implemented at the undergraduate level, and with the development of graduate education, the University had become an educationally diverse institution. Recognition of this further growth and development again resulted in an official change in name to Southwest Missouri State University.

In 1963, a residence center offering freshman and sophomore level courses was established at West Plains. Now, as a second campus of the university with its own mission, the West Plains campus offers a two-year general education program, which is fully integrated with programs on the main campus, as well as other specialty and skills courses.

In 2005, the University's name changed to Missouri State University. This final name change reflected the changing nature of the institution, as evidenced by increased enrollment, admissions standards, graduation rates, graduate programs and freshman success.

The State Fruit Experiment Station, established by a legislative act in 1899, is the oldest identifiable segment of Southwest Missouri State University. Until 1974, it operated as a state agency under a board of trustees appointed by the Governor. As a result of the Omnibus State Reorganization Act of 1974, administrative responsibility for the Station was given to the Board of Regents of the University. In 1984, the Station was assigned departmental status in the College of Health and Applied Sciences as part of a reorganization of the University. The most recent university mission statement identifies the Station as a separate campus with a research designation.