With their new-found wealth, Chuck (Zachary Levi) and Sarah Bartowski (Yvonne Strahovski) own the fictional big-box store Buy More, as well as their new freelance spy organization, Carmichael Industries, which includes John Casey (Adam Baldwin) and Morgan Grimes (Joshua Gomez).

[7] Series stars Zachary Levi, Yvonne Strahovski, and Adam Baldwin all expressed an interest to reprise their roles of former Special Agents Charles "Chuck" and Sarah Bartowski, and Colonel John Casey,[9] and an interview with Ryan McPartlin about the future of the series suggested he would also return as Dr. Devon "Captain Awesome" Woodcomb.

The big-box store Buy More, which Chuck purchased in the fourth-season finale, is also featured in the fifth season, with Mark Christopher Lawrence, Scott Krinsky, and Vik Sahay reprising their roles as Michael "Big Mike" Tucker, Jeffrey "Jeff" Barnes, and Lester Patel, respectively.

[8][11] It was confirmed at the 2011 San Diego Comic-Con that Sarah Lancaster would also reprise her role as Dr. Eleanor "Ellie" Bartowski Woodcomb.

[13] Brandon Routh returned to the series as Daniel Shaw, a villain that the team had previously defeated.

[15] Other recurring cast members include Bonita Friedericy as Brigadier General Diane Beckman, the head of the NSA and an ally to Carmichael Industries,[8] Mekenna Melvin as Alex McHugh, Casey's daughter and Morgan's girlfriend, and Richard Burgi as Clyde Decker, a CIA agent involved in a rogue operation to take down Chuck.

It was confirmed at the Comic-Con panel that Star Wars actor Mark Hamill would play a villain in the fifth-season premiere.

[16] Lost's Jeff Fahey and Smallville's Justin Hartley guest starred in the season's second episode, as Karl Sneijder, "the president and CEO of diamond giant Natal Jewelers," and his kidnapped brother Wesley, respectively.

[18] The fifth episode featured cameo appearances by Community's Danny Pudi[19] and Yvette Nicole Brown.