• Tom Hardy as Eddie Brock / Venom: An investigative journalist who is the host of Venom, an alien symbiote that imbues him with super-human abilities.^[5]
• Chiwetel Ejiofor as Rex Strickland: A commander for Imperium who is tracking Eddie and trying to capture Venom.^[6][7][8]
• Juno Temple as Dr. Teddy Payne: A scientist for Imperium, haunted by the death of her brother from a lightning strike that left her arm scarred, who becomes the host of a purple-colored, tendril-haired symbiote.^[8]
• Rhys Ifans as Martin Moon: A hippie and an alien enthusiast.^[9]
• Stephen Graham as Patrick Mulligan: A former police detective who was infected with a symbiote after encountering Carnage, but is left for dead by it before he is captured by Imperium. Graham also voices an unnamed green symbiote with whom Mulligan bonds.^[7]
• Peggy Lu as Mrs. Chen: A convenience store owner who befriended Eddie and Venom.^[10]
• Clark Backo as Sadie Christmas: A researcher for Imperium who temporarily bonds with the Venom symbiote and later becomes the host of a green-colored, four-tendril symbiote.^[11]
• Alanna Ubach as Nova Moon: Martin’s wife and fellow hippie.^[9]
• Andy Serkis as Knull: The creator of the symbiotes, who seeks Eddie and Venom’s codex to free himself.^[12][13] Director Kelly Marcel said about choosing Serkis, who directed Venom: Let There Be Carnage (2021), to play the character: “We knew on Venom 2 that he was going to be this [Knull] character, we should be able to bring the character into this movie.”^[14]

Additionally, Hala Finley and Dash McCloud portray Martin’s children Echo and Leaf Moon, respectively.^[15] Cristo Fernández reprises his role as the bartender from the Marvel Cinematic Universe (MCU) film Spider-Man: No Way Home (2021), as well as a version of the character from Venom’s universe.^[10][16] Reid Scott, who previously portrayed Dr. Dan Lewis in the first two Venom films, voices the head of Imperium; he is credited as Dan despite the character not appearing in the film.^[16]