Henderson State University has a unique history. The only Arkansas university which has been controlled by both church and state; it is the only public institution named for an individual. Of the nine Arkansas public universities, HSU is one of two originally established as four year, degree conferring institutions and is the second oldest university under state control. The university has operated for a century under six names: Arkadelphia Methodist College (1890 - 1904), Henderson College (1904 - 1911), Henderson Brown College (1911 - 1929), Henderson State Teachers College (1929 - 1967), Henderson State College (1967 - 1975) and Henderson State University (since 1975).

Henderson State University had its beginnings on November 6, 1889, when Arkadelphia civic leaders and members of the Methodist Episcopal Church, South, held a town meeting at the Church to discuss establishment of a Methodist college for Arkadelphia and south Arkansas. Leaders of the movement, however, became convinced that the interest of the community could best be served by securing Hendrix College, an established Methodist institution then subject to relocation. Arkadelphia's failure to secure Hendrix College resulted in implementation of the original plan.

The institution was founded on March 24, 1890, and was incorporated as Arkadelphia Methodist College. It was chartered as a four year, co-educational, baccalaureate liberal arts college. The College opened on September 3, 1890, with 110 students and 10 faculty members. The name was changed to Henderson College in 1904 to honor Charles Christopher Henderson, a Trustee and prominent local businessman. In 1911, the name was amended to Henderson Brown College to honor Walter William Brown, who was also a Trustee.

From its founding in 1890 until 1925, the College also operated an academy which provided instruction for students desiring high school courses and for those not prepared to enter the collegiate curriculum.

Henderson was a sister institution of Hendrix College. In 1929, the educational commission of the Arkansas Methodist Conference proposed that the two colleges be merged in Little Rock. However, through the efforts of Arkadelphia citizens and religious and political leaders of south Arkansas, the institution, then known as Henderson Brown College, was offered to the State of Arkansas. The Arkansas General Assembly enacted legislation (Act 46) to "establish a standard Teachers College in Arkadelphia," and Henderson became a daughter of the state.

At present, degree programs are offered through the Matt Locke Ellis College of Arts and Sciences, the School of Business, the Teachers College, and the Graduate School. In addition to its own degree program in nursing, Henderson also operates the only aviation degree program in Arkansas.

In 1951, Henderson became a graduate center for the University of Arkansas and, in 1955, instituted its own graduate program. The university now confers six graduate degrees: MAT, MBA, MLA, MS, MSE, and EdS.