J. F. Ade Ajayi was one of the pioneering students of Nigeria's premier university, University College, Ibadan, when it was established in 1948. He graduated in 1952, garnering the bachelor of arts (general) in history, Latin, and English. Between 1952 and 1955, Ajayi attended University College, Leicester, where he earned another bachelor of arts (first-class honors) in history. He proceeded to the University of London for a doctorate degree, which he obtained in 1958. Ajayi started his career from the grade of lecturer at University College, Ibadan, that year, becoming a full professor of history in 1963. He held visiting teaching and research appointments at the University of California, Los Angeles, and Stanford University, among others. He was head of the Department of History at the University of Ibadan from 1966 to 1969 and dean of the Faculty of Arts between 1964 and 1966. Between 1972 and 1978, Ajayi was vice chancellor (president) of the University of Lagos. He retired from the University of Ibadan in 1989.

In addition to his numerous awards and honors, which include honorary doctorates from the University of Birmingham and University College, Leicester, Emeritus Professor Ajayi is also a Nigerian National Merit Award winner. Other notable awards include the African Studies Association's Distinguished Africanist Award, Foundation Fellow of the Historical Society of Nigeria, Order of the Federal Republic of Nigeria (OFR), and Most Distinguished Alumnus (MDA) of the University of Ibadan.