A native of La Plata, Maryland, Buffington graduated summa cum laude from Harvard College in 1991 with a Bachelor of Arts degree in English and American literature and Afro-American studies. He was a Harvard College National Scholar and is a member of the Phi Beta Kappa Society. A Regents Fellow, Buffington earned a Master of Arts degree in American culture from the University of Michigan in 1994. While serving as an instructor at Michigan, Buffington developed and taught interdisciplinary undergraduate courses in history and ethnic studies.

After beginning his professional career as assistant director of the Harvard alumni association from 1994 to 1997, he worked in the University's development office from 1997 to 1999 with responsibility for strategic planning and fundraising for cross-disciplinary programs. As Assistant Provost for Interfaculty Programs from 1999 to 2002, Buffington supervised the operations of 10 interfaculty programs and centers.

Buffington served as Deputy Chief-of-Staff to the President and Provost. In addition to serving as Provost Steven E. Hyman's chief adviser and director of operations, he also managed the arts, humanities and social science portfolios on behalf of the Provost and oversaw financial, administrative and academic matters for several programs.

Named Harvard's Associate Provost for Arts and Culture and Director of Cultural Programs in 2005, Buffington oversaw arts activities and planning for the cultural elements of Harvard's new campus in Allston, Massachusetts. As the University's principal representative to arts and cultural institutions in the Boston region, he was responsible for overseeing Harvard's Tony-award winning American Repertory Theatre; the Harvard University Art Museums; and Villa I Tatti, Harvard's Center for Italian Renaissance Studies.

Prior to relocating from Boston to Philadelphia, Buffington served on the boards of the Passim Music Center, The Open Gate Foundation and the Boston Modern Orchestra Project.

Buffington is the President and Chief Executive Officer of The University of the Arts in Philadelphia, Pennsylvania. At 38 years old, Buffington is one of the youngest university presidents. He took office on August 15, 2007 and was formally inaugurated on April 18, 2008. One of a handful of openly gay university presidents, Sean Buffington, who leads the University of the Arts, has been open about his sexual orientation for his entire professional life.