Two new characters are introduced, both of whom want to take the Intersect. One is a beautiful, young female enemy agent that works in the Pita Palace next to the Buy More, and the other is a handsome CIA agent who is posing as an undercover police detective investigating a theft at the Buy More who wants to take Chuck into his custody. The former quickly blows Chuck's cover, while the latter kidnaps him and makes him vanish from his former life.
While coping with the realization that Sarah still has feelings for Bryce, Chuck must assume his toughest cover yet by going on a mission as Sarah's husband. The team must foil the plot of a politically connected counterfeiter, who may be endangering the lives of Anna, Morgan and Anna's parents. Both Morgan and Anna also find themselves in the cross hairs.
Chuck must learn to balance a real love life with his cover love life when he meets a charming young woman by the name of Lou. At the same time, his relationship with Sarah gets interesting when the duo must explain their sexual relations with Ellie and Captain Awesome on a double date. Meanwhile, there is trouble when someone is using truth poison in order to retrieve codes for nuclear facilities.
As Chuck is beginning to adapt to his new life as a spy, a doctor who could possibly "cure" Chuck is murdered. Chuck then begins a high-speed fight for his life, all while trying to decide which of his two new colleagues might be out to get him. Meanwhile, Chuck's sister Ellie invites Sarah to dinner to meet the family.