Fortnow received his Ph.D. in Applied Mathematics at MIT in 1989 under the supervision of Michael Sipser. Before he joined Georgia Tech in 2012, Fortnow was a professor at Northwestern University, the University of Chicago, a senior research scientist at the NEC Research Institute and a one-year visitor at CWI and the University of Amsterdam.

Fortnow's research spans computational complexity and its applications, most recently to micro-economic theory. His work on interactive proof systems and time-space lower bounds for satsifability have led to his election as a 2007 ACM Fellow. In addition he was an NSF Presidential Faculty Fellow from 1992-1998 and a Fulbright Scholar to the Netherlands in 1996-97.

Fortnow's survey The Status of the P versus NP Problem is CACM's most downloaded article. Fortnow has written a popular science book, The Golden Ticket: P, NP and the Search for the Impossible loosely based on that article.