Education on the college level first came to Wilmington in 1946 when a college center was established under the direction of the North Carolina College Conference and under the administration of the Directorate of Extension of the University of North Carolina at Chapel Hill. The center offered courses on the freshman level to some 250 students during the academic year 1946–47. In 1947, a tax levy was approved by the citizens of New Hanover County, and Wilmington College was brought into existence as a county institution under the control of the New Hanover County Board of Education. In 1948 Wilmington College was officially accredited by the North Carolina College Conference and became a member of the American Association of Junior Colleges. In 1952 the institution was accredited as a junior college by the Southern Association of Colleges and Schools.

In 1958, New Hanover County voted to place the college under the Community College Act of the state of North Carolina. By virtue of this vote, the college became a part of the state system of higher education, and control passed from the New Hanover County Board of Education to a board of 12 trustees, eight of whom were appointed locally and four of whom were appointed by the governor of the state. At the same time, the requirements for admission and graduation and the general academic standards of the college came under the supervision of the North Carolina Board of Higher Education, and the college began to receive an appropriation from the state for operating expenses in addition to the local tax.

On July 1, 1963, by an act of the General Assembly of North Carolina, Wilmington College became a senior college with a four-year curriculum, authorized to offer the bachelor's degree.

By vote of the Board of Trustees of the University of North Carolina in late 1968, with subsequent approval by the North Carolina Board of Higher Education, and by an act of the General Assembly of North Carolina in 1969, Wilmington College became, on July 1, 1969, the University of North Carolina at Wilmington. It, and the institution in Asheville previously designated as Asheville-Biltmore College, became the fifth and sixth campuses of the University of North Carolina.

On October 30, 1971, the General Assembly in special session merged, without changing their names, the remaining ten state-supported senior institutions into the university. Thus, the University of North Carolina now comprises 16 institutions.

On August 22, 1977, the Board of Governors of the University of North Carolina authorized the University of North Carolina at Wilmington to offer its first graduate programs at the master's level.

In the spring of 1985, the Board of Governors of the University of North Carolina elevated the University of North Carolina at Wilmington to a Comprehensive Level I University.

The programs offered by the university include four-year programs leading to the Bachelor of Arts, Bachelor of Music, Bachelor of Science and Bachelor of Social Work degrees within the College of Arts and Sciences, the Cameron School of Business, the Watson School of Education, and the School of Nursing; graduate programs leading to the Master of Arts, the Master of Arts in Teaching, the Master of Business Administration, the Master of Education, the Master of Fine Arts in Creative Writing, the Master of School Administration, the Master of Science, the Master of Science in Accountancy and the Master of Science of Nursing degrees; a variety of pre-professional programs, and special programs in a variety of areas, including marine science research, and continuing education.