The cast members of the original series reprise their roles, with the exception of Patrick Warburton, as his character is deceased in the series along with Wayne Knight's character; and followed by Stephen Furst, as he passed away on June 16, 2017. This series' cast members include Liliana Mumy and A. J. LoCascio as rookies Inez Galactic and Antilles Quasar, and Dave Foley as informative robot Assignment Droid.
Taking place five years after the original series, Buzz Lightyear had sacrificed himself to save the galaxy from Emperor Zurg's station by blowing it up, with Zurg along with it.
Team Lightyear member, Mira Nova, leads the remaining team members Booster Munchapper and XR on their further missions and adventures throughout the galaxy. Meanwhile, Zurg's former henchman, Warp Darkmatter, leads the remaining army of Zurg's to carry on his legacy.
- Adam Carolla as Commander Zeb Nebula
- Liliana Mumy as Inez Galactic
- A. J. LoCascio as Antilles Quasar
- Dave Foley as AD (Assignment Droid)
- Jeff Pidgeon as the Little Green Men
- Diedrich Bader as Warp Darkmatter
- Frank Welker as the Grubs, Corporal
- Francesca Marie Smith as Star Cruiser 43's computer voice
- Tara Strong as Bonnie Lepton
- Steve Hytner as Ty Parsec
- Phil LaMarr as Rocket Crockett
- John O'Hurley as King Nova
- Nikki Cox as Petra Hammerhold
- Kerri Kenney as Gravitina
- Conchata Ferrell as Ma Munchapper
- Jess Harnell as Clay, Gramps Munchapper
- Kevin Michael Richardson as Tremendor, Lardak Lurdak, Varg, Gargantia
- French Stewart as Rentwhistle Swack
Among the cast being hired to come back as their signature roles, the role for Booster Munchapper was given to veteran voice actor Sam Riegel due to the passing of Stephen Furst in 2017, while Rob Paulsen replaces John O'Hurley as Mira Nova's father King Nova, including Jeff Pidgeon reprising his role as the Little Green Men in place of Patrick Warburton.
Aside from Wang Film Productions, that was the animation provider for the previous series, the animation on this series is done by Rough Draft Korea.