In 1996, a young Cletus Kasady (Woody Harrelson) watches in despair as his beloved Frances Barrison (Naomie Harris) is removed from the St. Estes Home for Unwanted Children and sent to the Ravencroft Institute. Due to the escalating nature of her powers, authorities decide she must be relocated to a facility designed for the criminally insane. During the transfer, Frances unleashes her sonic scream, injuring young police officer Patrick Mulligan (Stephen Graham), who mistakenly believes he has killed her. Frances is subsequently taken to Ravencroft, her abilities confined.
Fast forward to the present, Mulligan, now a detective, requests investigative journalist Eddie Brock (Tom Hardy) to speak with Kasady, who is on death row at San Quentin State Prison. Mulligan suspects that Kasady may divulge the locations of his victims' remains exclusively to Brock. However, unbeknownst to them, Kasady’s message is a far more complex communication directed towards Frances, still imprisoned at Ravencroft.
After their visit, Brock's alien symbiote, Venom, deduces the location of the hidden bodies from Kasady's cryptic drawings, granting Brock a significant career milestone. This grisly discovery occurs at Rodeo Beach, California. Meanwhile, Venom expresses frustration with their diet of chocolates and subtly hints at its preference for brains, which Eddie steadfastly denies.
Brock also faces personal turmoil when his ex-fiancée, Anne Weying (Michelle Williams), informs him of her engagement to Dr. Dan Lewis (Reid Scott), further aggravating Venom's feelings. As Kasady, condemned to death, invites Brock to witness his execution, he recounts the heinous acts he has committed, including the deaths of his grandmother and mother. His tale intertwines with his love for Frances, who had been his savior and escape from torment.
After a heated exchange during another visit, Kasady provokes Venom, leading to a confrontation where Kasady bites Brock, assimilating a fragment of the symbiote. Following this, a significant clash between Brock and Venom ensues, resulting in Venom leaving Eddie and wreaking havoc. In an act of rebellion, Venom dismantles Brock’s prized possessions before embarking on its independent journey.
As Kasady's execution proceeds, a new red symbiote, Carnage, emerges, taking on a savage rampage within the prison, liberating inmates while slaughtering guards. With a clear vendetta, Carnage partners with Kasady to free Frances from Ravencroft, seeking vengeance against Brock and Venom. With increasing suspicion, Mulligan confronts Brock regarding the ensuing chaos linked to him.
The stakes escalate as Kasady and Carnage orchestrate a plan to locate Frances, leading to confrontations at significant locations tied to their troubled past, including the St. Estes orphanage. As tensions rise, Mulligan arrests Brock based on evidence of a monstrous presence following his track. In a timely twist of fate, Brock connects with Weying for legal support, and together they find Venom, reuniting with their symbiotic connection just in time to face the escalating danger.
The stage is set for an ultimate showdown as Kasady holds Mulligan captive while planning his wedding to Frances. In this chaotic climax, Brock and Venom match wits against Carnage, leading to shocking betrayals and a duel where ultimate sacrifices are made. As the dust settles, with both friendship and love challenged yet unbroken, Mulligan's fate remains uncertain with a flicker of light in his eyes.
As fugitives, Brock and Venom contemplate their next moves over a vacation, when an unexpected cosmic event hurls them into a riveting new adventure, watching J. Jonah Jameson reveal Spider-Man's true identity on television, hinting at the vast untapped multiverse that awaits them.
