Wounded to the brink of death and suffering from amnesia, Jason Bourne is rescued at sea by a fisherman. With nothing to go on but a Swiss bank account number, he starts to reconstruct his life, but finds that many people he encounters want him dead. However, Bourne realizes that he has the combat and mental skills of a world-class spy—but who does he work for?

A CIA operation to purchase classified Russian documents is blown by a rival agent, who then shows up in the sleepy seaside village where Bourne and Marie have been living. The pair run for their lives and Bourne, who promised retaliation should anyone from his former life attempt contact, is forced to once again take up his life as a trained assassin to survive.

Bourne is brought out of hiding once again by reporter Simon Ross who is trying to unveil Operation Blackbriar, an upgrade to Project Treadstone, in a series of newspaper columns. Information from the reporter stirs a new set of memories, and Bourne must finally uncover his dark past while dodging The Company's best efforts to eradicate him.

Edward Wilson, the only witness to his father's suicide and member of the Skull and Bones Society while a student at Yale, is a morally upright young man who values honor and discretion, qualities that help him to be recruited for a career in the newly founded OSS. His dedication to his work does not come without a price though, leading him to sacrifice his ideals and eventually his family.