Payton was United States Ambassador to the Republic of Cameroon in West Africa from 1967-69. His career also included nine years at Washington University in St. Louis, during five years of which he was Vice Chancellor for Development.

Payton was educated at the University of Chicago where he received a master's degree in history (his only earned degree). In 1988 the University of Chicago awarded him its Alumni Medal. Professor Payton received an honorary doctorate of Humane Letters from Indiana University in May, 2000. He holds honorary doctorates from Adelphi University, MacMurray College, York College of Pennsylvania, Quinnipiac College, and Rollins College. In 1984 he received the Distinguished Service to Education Award of the Council for Advancement and Support of Education.

Currently, Payton spends a significant amount of his time writing and lecturing on the subject of philanthropy for foundations, community groups, scholars, and students. He continues to lead the Jane Addams – Andrew Carnegie Fellows Program he founded in 1991. He has traveled extensively to Eastern Europe, and Northern Ireland to explore the role of philanthropy in resolving ethnic conflict and building civil society.