After the war ended, Compton resigned his chair as Charles H. Swift Distinguished Service Professor of Physics at the University of Chicago and returned to Washington University in St. Louis, where he was inaugurated as the universitys ninth chancellor in 1946. During Comptons time as chancellor, the university formally desegregated its undergraduate divisions in 1952, named its first female full professor, and enrolled record numbers of students as wartime veterans returned to the United States. His reputation and connections in national scientific circles allowed him to recruit many nationally renowned scientific researchers to the university. Despite Compton's accomplishments, he was criticized then, and subsequently by historians, for moving too slowly toward full racial integration, making Washington University the last major institution of higher learning in St. Louis to open its doors to African Americans.
Compton retired as chancellor in 1954, but remained on the faculty as Distinguished Service Professor of Natural Philosophy until his retirement from the full-time faculty in 1961. In retirement he wrote Atomic Quest, a personal account of his role in the Manhattan Project, which was published in 1956.