While exploring space for new habitable worlds, a probe belonging to the bio-engineering corporation Life Foundation discovers a comet covered in symbiotic lifeforms. The probe returns to Earth with four samples, but one escapes and causes the ship to crash in Malaysia. The Life Foundation recovers the other three and transports them to their research facility in San Francisco, where they discover that the symbiotes cannot survive without oxygen-breathing hosts, which often fatally reject the symbiosis. Investigative journalist Eddie Brock reads about these human trials in a classified document in the possession of his fiancée Anne Weying, an attorney preparing a lawsuit defense for the Life Foundation. Brock confronts Life Foundation CEO Carlton Drake about the trials, leading to Brock and Weying losing their jobs. Consequently, Weying ends their relationship.

Six months later, Drake's symbiosis trials are closer to success, though one of his symbiotes dies due to carelessness. Brock is approached by Dora Skirth, one of Drake's scientists, who disagrees with his methods and wants to expose him. She helps Brock break into the research facility to search for evidence, and he learns that an acquaintance of his, a homeless woman named Maria, is one of the test subjects. Brock attempts to rescue Maria, but the symbiote possessing her transfers to his body without him realizing, leaving her dead. Brock escapes and soon begins displaying strange symptoms. He reaches out to Weying for help, and her new boyfriend, Dr. Dan Lewis, discovers the symbiote on examining Brock. Drake exposes Skirth to the remaining captive symbiote, killing both. This leaves the symbiote inside Brock as the only known surviving specimen.

Drake sends mercenaries to retrieve the symbiote from Brock, but it manifests around his body as a monstrous creature that fights off the attackers. It later introduces itself to Brock as Venom and explains that the comet is searching for planets where the symbiotes can possess and devour the inhabitants. Venom offers to spare Brock if he helps the symbiotes achieve their goal, and Brock comes to enjoy the superhuman attributes that the symbiote imbues him with. Brock breaks into his old workplace to turn in evidence of Drake's crimes but is surrounded by SWAT officers. Weying sees him transform to escape and takes Brock to Lewis's office where they explain that the symbiote is rotting Brock's internal organs. Brock notes that the symbiote has two weaknesses: high-pitched noises and fire. Although Venom claims that the organ damage can be reversed, Weying uses an MRI machine to separate him from Brock, whom Drake's men then capture.