Chuck Bartowski (Zachary Levi) is a socially awkward twenty-something who works as a computer expert at the Nerd Herd at his local Buy More (a parody of Best Buy's Geek Squad), a local electronics retailer (a CompUSA store was used), with his best friend, Morgan Grimes (Joshua Gomez). Chuck's sister Ellie (Sarah Lancaster) is a doctor who is constantly looking out for his best interests and wants to help him find a girlfriend. Also joining the cast is Ellie's fiance, Devon "Captain Awesome" Woodcomb (Ryan McPartlin), also a doctor looking out for Chuck's social life.
On the night of his birthday party, Chuck receives an e-mail from his former Stanford University roommate, Bryce Larkin (Matthew Bomer), who is now a "rogue" CIA agent. When he opens it, the entire database of all the US government's secret information - a neural supercomputer called the Intersect - is subliminally embedded into his brain. Both the National Security Agency and the Central Intelligence Agency want the intelligence returned to them and dispatch agents of their own - Major John Casey (Adam Baldwin) and Sarah Walker (Yvonne Strahovski) - to retrieve that data.