In the 1890s, the University of Chicago, fearful that its vast resources would injure smaller schools by drawing away good students, affiliated with several regional colleges and universities: , , , and . In 1896, the university affiliated with in Mount Carroll, Illinois. Under the terms of the affiliation, the schools were required to have courses of study comparable to those at the university, to notify the university early of any contemplated faculty appointments or dismissals, to make no faculty appointment without the university's approval, and to send copies of examinations for suggestions. The University of Chicago agreed to confer a degree on any graduating senior from an affiliated school who made a grade of A for all four years, and on any other graduate who took twelve weeks additional study at the University of Chicago. A student or faculty member of an affiliated school was entitled to free tuition at the University of Chicago, and Chicago students were eligible to attend an affiliated school on the same terms and receive credit for their work. The University of Chicago also agreed to provide affiliated schools with books and scientific apparatus and supplies at cost; special instructors and lecturers without cost except travel expenses; and a copy of every book and journal published by the at no cost. The agreement provided that either party could terminate the affiliation on proper notice. Several University of Chicago professors disliked the program, as it involved uncompensated additional labor on their part, and they believed it cheapened the academic reputation of the university. The program passed into history by 1910.
In 1929, the university's fifth president, , took office; the university underwent many changes during his 24-year tenure. Hutchins eliminated varsity football from the university in an attempt to emphasize academics over athletics, instituted the undergraduate college's liberal-arts curriculum known as the Common Core, and organized the university's graduate work into four divisions. In 1933, Hutchins proposed an unsuccessful plan to merge the University of Chicago and into a single university. During his term, the University of Chicago Hospitals (now called the ) finished construction and enrolled its first medical students. Also, the , an institution distinctive of the university, was created.
The Maroons compete in the 's as members of the (UAA). The university was a founding member of the and participated in the Division I men's basketball and football and was a regular participant in the men's basketball tournament. In 1935, the University of Chicago reached the Sweet Sixteen. In 1935, player became the first winner of the . However, the university chose to withdraw from the Big Ten Conference in 1946 after University President de-emphasized varsity athletics in 1939 and dropped football. (In 1969, Chicago reinstated football as a Division III team, resuming playing its home games at the new .)