The Urbana-Champaign campus, founded in 1867, is the largest and most prestigious of the three. It is home to 16 colleges & instructional units including the College of Agricultural, Consumer and Environmental Sciences, College of Applied Health Sciences, Institute of Aviation,College of Business, College of Communications, College of Education, College of Engineering, College of Fine and Applied Arts, Graduate College, Institute of Labor and Industrial Relations, College of Law, College of Liberal Arts and Sciences, Graduate School of Library and Information Science, College of Medicine at Urbana-Champaign, School of Social Work, and the College of Veterinary Medicine.

It is also home to the National Center for Supercomputing Applications, NCSA, where Marc Andreessen (of Netscape fame) and others helped develop the Mosaic web browser, the first HTML browser capable of rendering images. In addition, in 1987, NCSA created NCSA Telnet, a program which permitted users access to the supercomputer's resources remotely. Also, in the movie 2001 A Space Odyssey, the ship's computer, HAL, was said to have been built in Urbana.

UIUC is also famous for its contributions in Electrical Engineering, and is the birth place of world's first light-emitting diode (LED). The library is notable for both being the largest public academic library in the country as well as possessing over ten million volumes. It is highly ranked in law, library and information science, architecture, political science, chemistry, engineering, electrical and computer engineering, computer science, physical sciences, advertising, psychology, labor and industrial relations, educational psychology, accounting, speech communication, and music. Physics professor John Bardeen won the Nobel Physics Prize twice in his lifetime, an honor no other researcher has received. The school's marching band, named the Marching Illini, also enjoys a superb reputation. The symbol of the University's athletic teams is a Native American figure, Chief Illiniwek, which has sparked significant controversy.

Currently the campus boasts the worlds most technologically advanced Computer Science building, Siebel Center.