Eddie Brock is struggling to coexist with the alien symbiote Venom, which grants him superhuman abilities in exchange for a steady diet of human brains which Eddie restricts to the brains of chickens and chocolate. While trying to revive his career as a journalist, he interviews the convicted serial killer Cletus Kasady, who becomes fixated on Eddie. During a visit to San Quentin prison, an altercation results in Kasady being accidentally infected with another symbiote, giving birth to a far more chaotic and destructive entity.

As the new symbiote, named Carnage, wreaks havoc, Eddie and Venom must navigate their fractured relationship to stop Carnage’s violent spree. Kasady's past and present collide as he seeks to reunite with his lost love, Frances Barrison, who harbors her own dark abilities. Together, Carnage and Frances pose a grave threat, pushing Eddie and Venom to their limits both in their capacity as guardians and as partners in an uneasy symbiosis.