Mississippi Valley State University is located in Leflore County, one mile northeast of Itta Bena, adjacent to U.S. Highway 82. The institution is located on a 450-acre tract of land. The site for the campus development consists of 200 acres.

Mississippi Valley State University is approximately five miles from Greenwood, which has a population of 18,906 and approximately 50 miles from Greenville, which as population of 45,226. The University is approximately 100 miles north of Jackson, and 120 miles south of Memphis, Tennessee. It is located in the heart of the Mississippi Delta where 34 percent of the black population of the state is located.