When Spider-Man spots his two main enemies, Venom and Carnage, hijacking on John Jameson's spaceship on a trip to the mysterious planet, Counter-Earth, he fails to stop them and the two symbiote villains go with Jameson to Counter-Earth, where the ship crashes and Jameson presumably dies. The public then blames Spider-Man for Jameson's seeming death. Spider-Man fakes his own death and lies low for half a year until he gets a new nano-tech costume from Reed Richards and gets another ride to Counter-Earth.

Spider-Man reaches his destination on Counter-Earth and finds out that John Jameson survived the crash. He has become a member of a rebellion fighting against the forces of the High Evolutionary, a figurehead who hates humans and creates animal-mutant hybrids called the Beastials. Spider-Man then joins the group and moves in with a single mother, Dr. Naoko Yamada-Jones, and her son, Shane Jones.

Spider-Man meets the Counter-Earth version of the Green Goblin, a hero who mistakes Spider-Man for a villain. Spider-Man realizes the kidnapper of Dr. Naoko Yamada-Jones isn't the Goblin. The two team up to save her and stop a plan by her kidnappers responsible for the green Bio-Mass: Venom and Carnage.

A member of the rebellion against the High Evolutionary, Git Hoskins, steals a bomb and threatens to blow up the Counter-Earth New York. The rebellion and the Beastials are forced to team up to get it back before both humans and Beastials will die.

A machine man, X-51 (the 51st off the assembly line), one of the High Evolutionary's operatives, refuses to hurt innocent people, so he betrays the Evolutionary and decides to join the rebellion.

When the High Evolutionary sees that Spider-Man is a bug in his plans, he has his minion, Sir Ram, hire an assassin named the Hunter (Counter-Earth's Kraven the Hunter) to kill Spider-Man.