At the outset of the show, Chuck Bartowski is presented as a twentysomething underachiever who works at the local Buy More in its Nerd Herd division (a fictionalized Geek Squad). Chuck's life stalled after his college roommate, Bryce Larkin, planted test answers under Chuck's bed and then reported him to the officials, which led to Chuck's expulsion from Stanford University in 2002 - only twelve credits shy of completing his bachelor's degree. He also lost the love of his life: college girlfriend, Jill Roberts. Following his expulsion, Chuck moved in with his sister and began working at the Burbank, California branch of Buy More. At some point over the next five years Chuck became the Nerd Herd supervisor. In the pilot, which picks up five years later, the viewers are introduced to the key persons in Chuck's current life: his older sister, Eleanor Fay "Ellie" Bartowski, M.D., her live-in boyfriend, Devon "Captain Awesome" Woodcomb and Chuck's best friend since childhood, Morgan Grimes. Little else is known about Chuck's family except that his mother left when he was in fifth grade and that his father Stephen Bartowski was "never really there," and left for good sometime before Chuck completed high school.

On his birthday in 2007, Chuck opens an email from Bryce Larkin that downloads the entire Central Intelligence Agency/National Security Agency database into his brain, a database known as the Intersect. Unbeknownst to Chuck, the Intersect computer has been destroyed, making his brain the only location of this top-secret information. The government learns that Chuck Bartowski was the last known person that Bryce Larkin contacted, and so both the CIA and NSA (independent of each other) send agents to find him. The CIA dispatches field officer Sarah Walker to find him, while the NSA sends Major (now Colonel) John Casey to assassinate him. The two agents eventually cross paths, and Sarah fends off Casey's assassination attempts when they discover that Chuck is a human version of the Intersect and sees a rapid-fire series of images (or "flashes") whenever he sees something that is in the Intersect database. The two agencies conclude that Chuck must be protected and assign Sarah and Casey jointly to the task.