Ohio Valley University, located between Parkersburg and Vienna, was a private liberal arts institution allied with the Church of Christ. In 1957, a group from West Virginia and Ohio purchased 132 acres between Parkersburg and Vienna for the purpose of establishing a college with an independent board of trustees composed of members of the church.

The institution was chartered February 28, 1958, and began operation as a junior college September 12, 1960. The first classes were held in temporary facilities in South Parkersburg. Beginning in 1963, new buildings were occupied on the permanent campus, where an administration and library building, the Ethel Merritt Erickson Theater, three dormitories, a dining hall, a student union, and an activity center (later known as the South Campus) were located.

Ohio Valley College expanded in 1994 by purchasing an adjacent property, the former St. Joseph's Seminary, creating a 250-acre campus. Two dormitories, a commons area, Stotts Administrative Center, Isom Academic Center, gymnasium, dining hall, a student center, and baseball and soccer fields occupied the North Campus.

The first president, Don Gardner, led the college from 1959 to 1964. He was succeeded by E. Lewis Case, 1965-66. Ohio Valley College was accredited by the state of West Virginia in 1965 and by the North Central Association of Colleges and Schools in 1978. A baccalaureate degree in Bible was added in 1981. In 1993, the North Central Association approved baccalaureate degrees in business administration, elementary education, liberal studies, and psychology. In 1998, additional business degrees in accounting, management, human resource management, and marketing were approved. In the 21st century, the school also offered secondary education programs in English, mathematics, natural sciences, physical education, and social studies, as well as a certification in special education.

The college operated the Institute for Adult Learning on the South Campus, from which adult learners could complete a B.S. degree in organization management and an associate degree in professional studies. There was an English as a second language program in the summertime to accommodate foreign students. The college managed Noah's Harbor Daycare Center for the children of faculty, staff, and students. Ohio Valley College prepared students for the Christian ministry, among other professions.

In 1993, Ohio Valley College was consolidated with Northeastern Christian Junior College of Villanova, Pennsylvania, which closed its campus. Faculty and trustees of Northeastern Christian also joined the Ohio Valley College. In 2005, Ohio Valley College changed its name to Ohio Valley University. The institution had an enrollment of more than 500 students at the time.

President James Marvin Powell served the college from 1966 to 1969, succeeded by Justin B. Roberts, 1970-77. E. Keith Stotts, the longest serving president, led the college from 1977 to 1998. Robert W. Stephens Jr., an Ohio Valley College alumnus, followed Stotts, and James A. Johnson became president in 2005. Stotts, who had taken the title of chancellor, resumed the office of president in April 2009. Harold Shank was named president of Ohio Valley in 2011. Michael Ross was president and Stotts was chancellor at the time of the school’s closure.

The college struggled financially for years, and in the summer of 2020, a multistate college accrediting agency put the school on probation over its lack of resources. In summer 2021, the school’s computer servers went down, evidently erasing all grades and transcripts of current and former students. In December 2021, the university’s governing board voted to stop offering classes. The state Higher Education Policy Commission then revoked the school’s right to award degrees or enroll new students. The last graduation was held in May 2022. The school had 170 students, including about 30 seniors, when it closed.