John and his wife Kathy DeStefano met at the University of Connecticut as undergraduates, where he also earned a Masters in Public Administration.

He served ten consecutive terms, (posting his tenth mayoral election victory in November 2011) during which his efforts included a massive overhaul of New Haven's public schools, based principally on the magnet school model, and New Haven's selection as a federal "Empowerment Zone".

DeStefano and Glassman were defeated by the very popular incumbent governor Jodi Rell and her runningmate Michael Fedele in the general election by one of the largest majorities in state history[8] and conceded that night.

[10] DeStefano focused his tenure as mayor on improving education and public safety in New Haven, as well as on economic development.

Justice Samuel Alito's concurring opinion suggested that DeStefano had been motivated by improper political considerations in denying the promotions.

[12] DeStefano currently teaches an undergraduate seminar, entitled "Making Public Choices in New Haven", at Yale University.