Following a history degree and graduating from both Sciences Po and ENA, Védrine had toyed with the idea of entering journalism but, on the advice of the historian and family friend Jean Lacouture, instead took a post at the culture ministry.

Védrine popularized the neologism hyperpower to describe what he saw as the historically-unparalleled influence and might that were held by the United States at the turn of the century.

In 2005, he was appointed by UN Secretary-General Kofi Annan, a member of the High Council for the Alliance of Civilizations, an initiative that seeks to galvanize international action against extremism through intercultural and interreligious dialogue and cooperation.

Védrine is the author of more than 19 books, two of them having been translated in English by Philip H. Gordon: France in an age of globalization, co-authored with Dominique Moïsi (publisher: Brookings Institution Press, 2001) and History strikes back : how states, nations, and conflicts are shaping the twenty-first century (publisher: Brookings Institution Press, 2008), co-authored with Adrien Abecassis and Mohamed Bouabdallah.

Around the 2017 elections, news media reported that later President Emmanuel Macron sought regularly the advice of Védrine on foreign policy issues.