A space shuttle piloted by J.J.'s son, John Jameson, crash lands on the Tri-Borough Bridge carrying two strange meteors -- One that could provide a new nuclear fuel and one that contains an alien substance. The first is stolen by the Kingpin's henchman, the Rhino, just as Spider-Man arrives to save Jameson and the co-pilots. When the Rhino sends the aircraft off the bridge, Spider-Man emerges from the water with a dark stain covering his costume. Exhausted, he heads for home, only to awaken hanging from a skyscraper, now clothed in a black version of his costume.

Spider-Man goes after Eddie Brock for labeling him as he is now being stalked by bounty hunters at every turn. After being reassured by Mary Jane that he has changed, he seeks help from Dr. Curt Connors who discovers that the suit is alive!! And Peter is the host organism!

The Kingpin is furious at Spidey and sends the Shocker and later the Rhino out to finish him off with the aid of another new invention of Alistair Smythe. Meanwhile, Eddie Brock, as the symbiote creature Venom, is busy playing cat and mouse with Spider-Man, intruding on Peter's private life and making it clear he knows the web-slinger's secret identity. Peter soon realizes that the pumped-up Eddie as Venom is stronger than he is. Worse than that: Spidey's spider-sense doesn't work around him!

El simbionte de Venom regresa a la Tierra y se reúne con Eddie Brock. Dormammu le ordena a este robar el dispositivo interdimensional de Empresas Stark, capaz de liberar a Dormammu de su dimensión. Spiderman y Máquina de Guerra luchan contra Venom, que es derrotado. Pronto los villanos reciben ayuda de Cletus Kasady, que se ha unido a otro huésped.

Barón Mordo y Dormammu ayudan al compañero de Eddie Brock, Cletus Kasady, a transformarse en Carnage. Dormammu utiliza a Carnage para traerlo a esta dimensión. Iron Man y Spiderman trabajan juntos para derrotar a los simbiontes.