Determining which educational institution has claimed the most Nobel Prizes is somewhat complex. If one looks strictly at the number of laureates who have won Nobel Prizes while on the faculty of an institution, the clear winner is Harvard University of Cambridge, Massachusetts, with 32 Nobel Prize laureates from the faculty of Harvard University, the Harvard Medical school, and Harvard's labs in the history of the University until 2006. However, the University of Chicago in Chicago, Illinois, claims the most Nobel Prizes awarded to faculty, former faculty, and alumni. Affiliates of the University of Chicago have won Nobel Prizes in every field except Peace, with the highest number of laureates in Physics. Seventy-nine laureates in total with ties to the University of Chicago have won Nobel Prizes, and the University touts itself as “Nobel Alley.”

The University of Chicago's first Nobel Prize went to Albert Michelson in 1907 for Physics. Michelson was incidentally the first American to win a Nobel Prize. Michelson won for his work on measurements of the speed of light.

A number of Chicago's Nobel Prizes have been related to nuclear physics, quantum mechanics, and particle research. One of the researchers involved in the Manhattan Project, Enrico Fermi, took home a prize for Physics in 1938. Altogether, 27 individuals associated with the University of Chicago have gone to Sweden to receive Nobel Prizes in Physics.

In Economic Sciences, 23 Nobel Prizes have been awarded to University of Chicago affiliates, beginning with Paul Samuelson in 1970. Other economic winners have included Theodore Schultz, who did extensive research on the economics of developing nations, and Edward Prescott in 2004 for substantial contributions to the body of knowledge on macroeconomics. A number of University of Chicago affiliates have also been recognized for their work on decision-making within economic organizations.

Between 1934 and 2006, the University of Chicago laid claim to fifteen Nobel Prizes in Chemistry, starting with Harold Urey for his work on heavy hydrogen and including Willard Libby, developer of carbon-14 dating, and Paul Crutzen for his work in atmospheric chemistry. In Physiology or Medicine, 11 laureates have been affiliated with the University of Chicago, including Edward Doisy in 1943, who discovered Vitamin K, Hermann Muller in 1946, who linked x-ray radiation with mutations, and James Watson in 1962 for his work on DNA – it should be noted that Watson was working at Harvard University at the time. In Literature, three University of Chicago alumni have won Nobel Prizes: J.M. Coetzee, Saul Bellow, and Bertrand Russell.