Greene was drawn to mathematics at an early age. He could multiply 30-digit numbers before he entered kindergarten, and by sixth grade his math skills had advanced beyond the high-school level. He attended Harvard University and graduated summa cum laude with a B.S. (1984) in physics. As a Rhodes scholar, he attended the University of Oxford, where he earned a physics Ph.D. (1987). He joined the physics faculty of Cornell University in Ithaca, N.Y., in 1990, and in 1996 he moved to Columbia University in New York City, where he became a full professor in both the physics and mathematics departments. At Columbia in 2000 Greene also became codirector of the university's Institute for Strings, Cosmology, and Astroparticle Physics.

Greene's wit and gift for using simple examples from everyday life to explain highly complex and abstract theories were largely responsible for the enormous success of the 2003 Public Broadcasting Service (PBS) special The Elegant Universe, a three-hour documentary on string theory hosted by Greene and based on his 1999 book of the same name. A finalist for the Pulitzer Prize, the book rose to fourth place on the New York Times best-seller list. Greene's second book, The Fabric of the Cosmos: Space, Time, and the Texture of Reality (2004), also was a best seller, and it spent 25 weeks on the Times list.