Duke University was created in 1924 by James Buchanan Duke as a memorial to his father, Washington Duke. The Dukes, a Durham family who built a worldwide financial empire in the manufacture of tobacco and developed the production of electricity in the two Carolinas, long had been interested in Trinity College. Trinity traced its roots to 1838 in nearby Randolph County when local Methodist and Quaker communities joined forces to support a permanent school, which they named Union Institute. After a brief period as Normal College (1851-59), the school changed its name to Trinity College in 1859 and affiliated with the Methodist Church. The college moved to Durham in 1892 with financial assistance from Washington Duke and the donation of land by Julian S. Carr. In December 1924, the trustees gratefully accepted the provisions of James B. Duke's indenture creating the family philanthropic foundation, The Duke Endowment, which provided, in part, for the expansion of Trinity College into Duke University.

As a result of the Duke gift, Trinity underwent both physical and academic expansion. The original Durham campus became known as East Campus when it was rebuilt in stately Georgian architecture. West Campus, Gothic in style and dominated by the soaring 210-foot tower of Duke Chapel, opened in 1930. East Campus served as home of the Woman's College of Duke University until 1972, when the men's and women's undergraduate colleges merged. Both men and women undergraduates attend Trinity College of Arts and Sciences and the School of Engineering. In 1995, East Campus became the home for all first-year students.

Academic expansion of the university included the establishment of new graduate and professional schools. The first B.D. degree was awarded in 1927, the first Ph.D. in 1929 and the first M.D. in 1932. The School of Law, founded in 1904, was reorganized in 1930 and given its own building on West Campus. The business school was founded in 1969 and named the Fuqua School of Business in 1980. The School of Forestry and Environmental Studies was founded in 1938 and was named the Nicholas School of the Environment in 1995.

Modern times have seen Duke realize its founder's aspirations to become a major center of learning. The Duke University Medical Center has achieved international prominence, and many Duke schools and departments are consistently ranked among the nation's best. The university frequently wins attention for its research achievements and academic innovations.