For more than a century, the University of Illinois at Chicago has had an extraordinary history, for it truly evolved out of the needs of the people of Illinois. The University of Illinois at Chicago traces its origins to several private health colleges founded during the late nineteenth century, including the Chicago College of Pharmacy, which opened in 1859, the College of Physicians and Surgeons (1882), and the Columbian College of Dentistry (1891).

The University of Illinois was chartered in 1867 in Champaign-Urbana, as the state's land-grant university. The Chicago-based health colleges affiliated with the University in 1896-97, becoming fully incorporated into the University of Illinois in 1913, as the Colleges of Medicine, Dentistry, and Pharmacy. Medical education and research dramatically expanded in the succeeding decades, leading to the development of several other health science colleges, which were brought together as the Chicago Professional Colleges of the University of Illinois. In 1961, these colleges became the University of Illinois at the Medical Center (UIMC). 

Following World War II, the University of Illinois increased its presence in Chicago by creating a temporary, two-year branch campus, the Chicago Undergraduate Division. Housed on Navy Pier, the campus accommodated primarily student veterans on the G.I. Bill. The campus was not a junior college, but rather had a curriculum based on Urbana's courses, and students who successfully completed the first two years requirements could go on to Urbana and finish their degree.

Classes at Navy Pier began in October 1946, and each semester around 4,000 students enrolled. As Chicago had no comprehensive public university at that time, most students were first generation college students from working families, who commuted from home. Demand for a public university education in Chicago remained high, even after the first wave of veterans passed, so the University made plans to create a permanent degree-granting campus in the Chicago area. After a long and controversial site decision process, in 1961, Mayor Richard J. Daley offered the Harrison and Halsted site, in Chicago's historic Near West Side, for the new campus.

Named the University of Illinois at Chicago Circle (UICC), the new campus opened in February 1965. Unlike the Navy Pier campus, Circle was a degree-granting institution, with ambitions to become a great university. Many of the newly recruited faculty came because it was connected to a strong research university and they pushed for rapid development into a research-oriented school emphasizing graduate instruction. Within five years of the campus' opening, virtually every department offered graduate degrees.

In 1982, the Medical Center and Circle Campus consolidated to form the University of Illinois at Chicago (UIC). This merger strengthened the University's potential for scholarly excellence, and pushed UIC to Carnegie Research 1 institution status in 1987.

UIC launched its latest initiative in 2000, the development of South Campus, providing increased resident living space and research facilities. Through its history, UIC has been a leader in the development of a new model of higher education: the comprehensive urban research university.