Wilkes University was first established in 1933 by Bucknell University under the name Bucknell University Junior College (BUJC) in Wilkes-Barre.Frank G. Davis, chair of the Education department at Bucknell, first developed the idea of BUJC and served as an early liaison between BUJC and Bucknell. BUJC attracted many students who were the first members of their families to benefit from higher education as the need for junior colleges arose in urban areas. The college opened in downtown Wilkes-Barre, where the first classes were held on the third floor of the Wilkes-Barre Business College building. By 1934, the business college moved out of the building and BUJC had taken it over and continued to grow over the years, acquiring old mansions for student housing, classrooms, and administration offices along the streets of South River and South Franklin.By 1945, the Board of Trustees formally moved to develop the junior college into a four-year institution.
In 1947, Wilkes College was instituted as an independent, nondenominational four-year college, with programs in the arts, sciences, and a number of professional fields, as well as numerous extracurricular activities. The student body in the postwar period was primarily composed of Luzerne County residents, especially G.I. bill recipients. In the 1950s, increasing numbers of students elected to live on campus, which led to a rapid expansion in on-campus student housing. Increased federal funding for science and engineering in the 1950s led the college to develop academic programs in those areas, build the Stark Learning Center, and increase enrollment.
Wilkes College became Wilkes University in December 1989, and the school officially received university status a month later, in January 1990.