Casting.

Zachary Levi and Adam Baldwin were the first two to be cast in February 2007 in the roles of Chuck Bartowski and veteran NSA agent Major John Casey, respectively. Fedak always had Baldwin in mind for the role of John Casey and the producers found that the actor was a "perfect fit" for the character during the first casting session.

Relative newcomer Yvonne Strahovski, an Australian, was chosen for the female lead role of CIA officer Sarah Walker in the same month.Casting continued throughout March with Sarah Lancaster, Joshua Gomez, and Natalie Martinez landing the parts of Dr. Ellie Bartowski (Chuck's older sister), Morgan Pace (Chuck's best friend), and Kayla Hart (Chuck's neighbor and love interest), respectively. The Kayla Hart character was dropped before filming because creators Chris Fedak and Josh Schwartz found it unlikely and too complicated to the storyline that two women would be pining over Chuck. Morgan's surname was later changed to "Grimes" and Sarah's surname was changed to "Walker" as it was previously "Kent".

On September 14, 2007, Rachel Bilson, of The O.C. (which executive producer Josh Schwartz also created) signed on for a multi-episode arc which aired in late October 2007.

On November 24, 2008, TV Guide reported that Tricia Helfer will join the show as Chuck’s new handler.