Main

• Karan Soni as Stewart Lipinski:
  The captain of the Cruiser. Enthusiastic and optimistic, Stewart desires to keep his crew's morale high and make new discoveries. As he laments in the final episode, he appears to be the only member of the crew eager to explore the universe. He often finds himself in conflict with his older sister Karen due to their clashing personalities and her resentment towards him being named captain over her. He also harbors unrequited feelings for Tina, with his failure to win her love being a recurring theme in the show. Series creator Paul Feig described Stewart as a smarter and intuitive teenage version of himself, with his enthusiasm being his greatest skill.^[3] Roni Akurati portrays Stewart as a child.
• Bess Rous as Karen Lipinski:
  The first officer of the Cruiser. Unlike her younger brother Stewart, Karen is stern, temperamental, and unconcerned with what others think of her. She resents Stewart for constantly getting what she feels she deserves to have, including being the vessel's captain, but also admits that he deserves his successes. Michael believes that she harbors romantic feelings for him, which is proven true when they enter into a relationship. In the last episode, Stewart names her captain when he leaves the ship and the two end up serving as co-captains when he returns. Feig noted that while Karen is an overachiever, she is passed up in favor of her brother due to having "terrible people skills" in contrast to Stewart's "good people skills".^[3]
• Eugene Cordero as Michael Newman:
  The second officer of the Cruiser. He is Stewart's best friend, whom he babysat when they were children. Michael often feels ignored and disrespected by the rest of the crew, which is compounded by humiliations frequently inflicted on him throughout the series. Despite the neglect, he shares a mutual attraction with Karen, leading to a relationship between the two. After he loses his left leg during a mission, he utilizes a cybernetic implant for the remainder of the show. According to Feig, Michael is based on his own friend who had been his babysitter.^[3] Sean-Ryan Petersen portrays Michael as a child.
• Milana Vayntrub as Tina Shukshin:
  The navigator of the Cruiser. Tina is established as being unqualified for the position and was hired because of Stewart's unrequited love for her, although she is the only member of the crew capable of mining extractions. Flighty and possibly unstable, she has a tendency to resort to violence. Tina also cares about her friends and loved ones, however, as demonstrated when she sets up a date between Natasha and Kent. Vayntrub said she was drawn to the show because of her interest in science, being able to engage in improvisational comedy, and the opportunity to work with Feig.^[4]
• Neil Casey as Kent Woolworth:
  The science officer of the Cruiser. The son of UMP Chairwoman Helen Woolworth, Kent was born as an organ donor for his older brother Derek and has spent most of his life nearly-comatose in a chemical bath. Only recently freed from the chemical bath after Derek's death, Kent's upbringing has left him with difficulty understanding basic social conventions and expressing emotions. His anatomy was also altered by his upbringing, causing him to have gills on his neck and no fingerprints, among other unusual features. He gradually falls in love with Natasha and in the finale, transfers his mind into the ship to physically be with her. Feig originally envisioned the role for Martin Starr as a "really dysfunctional nerd whose father married a younger woman and the new wife wanted the kid out of the house", but the character was changed following development of the pilot episode and the casting of Casey.^[3]
• Conor Leslie as Natasha:
  The computer of the Cruiser. Natasha was created as a hospitality bot for the inaugural Hooters Casino Space Shuttle before she was purchased by UMP. She is upbeat and polite, but is also capable of expressing a wide variety of human emotions, including anger and sadness. Among her desires is free will and she is ultimately granted human privileges by Stewart and Karen, although she continues to loyally serve her superiors. During her time on the ship, she develops romantic feelings for Kent and the two enter into a relationship. Feig said that he was inspired by "the idea of the friendly operating system who’s still insecure, like all of us" when writing Natasha.^[3]
• Joel Hodgson as Zalian Fletcher:
  The longtime engineer of the Cruiser. Prolonged exposure to radiation has left him in a permanently-impaired state, but he remains capable at his job and demonstrates resourcefulness when the ship loses power, helping guide Stewart through the crisis. His best friend on board the Cruiser is A.R.T. Feig stated that he always envisioned Hodgson as Zalian, whose casting reunited him with his Mystery Science Theater 3000 co-star Beaulieu.
• Trace Beaulieu as the voice of A.R.T.:
  A robot stowaway residing on the Cruiser. Appearing as a wisecracking friend and companion of Zalian, A.R.T. is really billionaire inventor Howard Barnes, who transferred his brainwaves into a robotic body. Numerous models of A.R.T. are stored on the ship and if a model is destroyed, a new model containing the memories of the previous model replaces it. As with his Mystery Science Theater 3000 co-star Hodgson, Beaulieu was Feig's original choice for the character.^[3] Beaulieu and Sherry O'Connor serve as the puppeteers for A.R.T.

Guest

• Jessica Chaffin as General Hayson: A high-ranking UMP official
• Björn Gustafsson as Ted Zachariasen: A military officer and Tina's boyfriend
• Mo Collins as Helen Woolworth: The chairwoman of UMP and Kent's mother
• Sarah Baker as Alien: A mysterious extraterrestrial who comes into contact with the crew
• John Milhiser as the voice of Coffee Bot: A robot who provides coffee on the ship. Ian O'Connor serves as the puppeteer for Coffee Bot.
• Dave Franco as Chad Sampson: A manipulative alien posing as the auxiliary deck officer. Franco went uncredited for the role.

Edgar Blackmon, Kate Comer, and Evan Gaustad portray members of Stewart's crew during a training exercise.