• Seth Rogen as Frank Frankfurter, a sausage
• Kristen Wiig as Brenda Bunson (season 1), a hot dog bun and Frank's love interest
• Michael Cera as Barry, a small deformed sausage and Frank's best friend
• Edward Norton as Sammy Bagel Jr., a neurotic Jewish bagel who had a relationship with Lavash. After Lavash's death, he becomes a comedian talk show host for Foodtopia.
• Will Forte as Jack, a surviving human whom Frank and Brenda kept alive in order to learn about humanity, along with things such as weather, ravenous animals, and politics. Due to becoming an ally of food, he resorts to cannibalism to avoid eating them.

• Sam Richardson as Julius, a tyrannical orange who uses his charms and wealth of human teeth to gain followers in order to take over Foodtopia.^[4] The character is a parody of Donald Trump, with his name being a play on Orange Julius and Julius Caesar.
• Yassir Lester as Iced Tea, a glass bottle of iced tea who is one of the recruits of a task force established by Barry in order to stop foods from stealing teeth from other foods. He also became Barry's partner during the task force establishment.
• Natasha Rothwell as Rutabaga Ginsberg, a rutabaga who serves as the judge of Foodtopia. Her name is a pun on former U.S. Supreme Court Justice Ruth Bader Ginsburg. Rothwell also voices multiple other characters, such as Margarine Taylor Greene (a margarine whose name is a pun on Marjorie Taylor Greene), Eggetha, Box of Crackers, Jar of Jams, and Pie.
• David Krumholtz as Kareem Abdul-Lavash, a Middle Eastern lavash who had a relationship with Sammy and is named after basketballer Kareem Abdul-Jabbar. He is killed off during the uprising, leaving Sammy devastated. Krumholtz also voices multiple other characters, such as Can of Peaches, Bread, Macaroni, Dog Food, and Tomato Soup.
• Scott "Diggs" Underwood as:
  • Gum, a Stephen Hawking-esque intelligent but paraplegic wad of chewed gum who wears glasses and has a mechanized wheelchair.^[5] He dies after sacrificing himself for the other food during the flood.
  • Twink, a twinkie who serves as a member of the "non-perishable immortals" who informed Frank about the truth of his world in the 2016 feature film. He is the only member of the trio of non-perishables who was confirmed to have returned from the film.
  • Duncan Doughnut, a double vanilla frosting-glazed doughnut whose name is a pun on the brand Dunkin' Donuts. He briefly replaces Sammy as show host for Foodtopia and as the owner of the Aesop's Cables (a pun on Aesop's Fables) electronics store under Julius' control, and later participates in a rebellion against Frank and Jack.
• Jimmy O. Yang as multiple characters, including Energy Drink, Licorice Rope, and Bread.
• Timothy Simons as multiple characters, including Strawberry Jam, Fruit, Potato, and Cop 3.
• Grey DeLisle as multiple characters, including Red Lentils (a box of red lentils who had a human tooth stolen by Pops), Katy Perrier (a bottle of Perrier—the brand of carbonated mineral water—and a play on the real-life singer Katy Perry), Carrot, Whole Milk, and Wild Berries.
• André Sogliuzzo as multiple characters, including Christopher "Chris" Bologna (a bologna who serves as one of the recruits of Barry's task force and later one of Julius' two enforcers, and whose name is a pun on actor Christopher Meloni, known for Law and Order: SVU), Melon Gibson (a melon whose name is a pun on actor Mel Gibson), and A1 Sauce.
• Jill Talley as multiple characters, including Kishka Hargitay (a kishka who serves as one of the recruits of Barry's task force and later one of Julius' two enforcers, and whose name is a pun on actress, producer and philanthropist Mariska Hargitay, also known for Law and Order: SVU), Wild Berries, and Random Foods.

Rogen had expressed interest in making a sequel to Sausage Party and more animated films aimed for adults. When asked about the possibility of a sequel, Rogen stated: "It's something we talk about, yeah. That's one of the reasons why we took away the [original] ending^[7] because we thought, well, if that was the first scene of the next movie it's probably not what you would want it to be, with them just seeing us and finding us basically. But the idea of a live-action/animated movie, like a Who Framed Roger Rabbit?-style hybrid, is also very exciting, mostly because Who Framed Roger Rabbit? is one of my favorite movies of all time."^[8]

On October 26, 2022, it was announced that Amazon had ordered a sequel from Point Grey Pictures, Annapurna Television, and Sony Pictures Television the co-writers Kyle Hunter and Ariel Shaffir returning to develop and executive produce the series under their production company Shaffirwhich while some of the cast (including Rogen, who co-wrote, co-produced, and created the film alongside creative partner Evan Goldberg) returning to reprise their roles, along with new members like Will Forte, Natasha Rothwell, Sam Richardson and Yassir Lester.^[9]

Unlike the first film being produced by Nitrogen Studios, the animation for the series was handled by Bardel Entertainment^[10] and Stellar Creative Lab.^[11] Co-producer/co-director Conrad Vernon returns as a supervising director.^[12]