It's 1947 and John Nash (RUSSELL CROWE) is a brilliant mathematician who's won a scholarship to attend Princeton and study under Professor Helinger (JUDD HIRSCH). While his fellow classmates, Richard Sol (ADAM GOLDBERG), Bender (ANTHONY RAPP) and Martin Hansen (JOSH LUCAS) don't deny his intelligence, they do find him and his obsessive quest to think differently as peculiar. Charles Herman (PAUL BETTANY), his charismatic roommate, however, gets along fine with him as he tries to get John to have some fun.
John eventually comes up with a revolutionary economic theory that lands him a job at the MIT campus of Wheeler Defense Labs where he, Sol and Bender work as contractors for the U.S. Government. One such job occurs in 1953 at the Pentagon where John is asked to break some Soviet codes. Seeing how good he is at that, covert agent William Parcher (ED HARRIS) of the Department of Defense puts John on a top-secret case to find hidden Soviet code regarding smuggled nuclear arms.
Told by Parcher to lead his normal life while carrying out his mission, John learns that part of his duties at Wheeler involve teaching. It's while doing just that that he meets Alicia Larde (JENNIFER CONNELLY), an opinionated and beautiful physics student. It's not long before the two become an item, much to the surprise of Charles who occasionally visits with his young niece, Marcee (VIVIEN CARDONE).
Yet, as time passes and John becomes increasingly paranoid due to his covert activities becoming more precarious, Alicia calls in Dr. Rosen (CHRISTOPHER PLUMMER) to assess his mental stability. From that point on, John and the others try to figure out if he's truly doing what he says or simply has been leading a delusional life.