In Metropolis, Superman has an encounter with a stories-tall robot controlled by Lex Luthor. After a short battle, Lex, in his robot steals a small programming circuit from S.T.A.R. Laboratories and then escapes. After thinking about his fight with Lex, Superman traces the path of the robot to the Metropolis Bay. After locating and entering Lex's underwater lab, Superman and Lex battle again. While Superman is disabled by a red sun-based laser blast to his eyes, Lex places the stolen programming circuit in a tube which is then transported to a hidden location. After he recovers, Superman captures Lex Luthor and has him imprisoned.
In New York, Spider-Man comes across a gang, working for Dr. Octopus, burglarizing the Metropolitan Museum. After his ground crew is beaten, Dr. Octopus steps in to fight Spider-Man. After a considerable fight between the two, Spider-Man is knocked out by a strike from the Flying Octopus. Spider-Man and Ock have a second encounter when Spider-Man's spider-sense detects trouble from a passing blimp. After falling through the blimp's false surface, Spider-Man discovers the Flying Octopus inside. After the fight, an unconscious Dr. Octopus is taken into custody by the police.
The villains from these two encounters meet when Lex and Ock wind up in a prison in Deming, New Mexico. The two escape the prison after Lex puts his plan into action.
The heroes from those two encounters cross paths at the World News Conference. Clark Kent, Lois Lane, Peter Parker, Mary Jane and their coworkers all attend the conference. It is during a discussion between Lois Lane and Peter Parker that a fake Superman shows up and abducts Lois and Mary Jane. Both Peter and the real Clark Kent are surprised by the abduction and both change to their hero identities. The heroes confront one another and Spider-Man, after receiving a red sun radiation blast from the hidden Lex is able to knock Superman around with very little effort. Even though Spider-Man realizes he's stronger than he used to be he decides his success is due to Superman's overstated reputation. After the radiation wears off and Spider-Man is unable to do anything more than injure himself in his attempt to subdue Superman the two heroes speak and realize they've been tricked.
The heroes track the villains first to a warehouse then to a village near Mount Kilimanjaro and finally to a satellite that was used by the Injustice Gang. It is from this satellite that Luthor takes over Comlab--which has an onboard high-intensity laser probe--by using the S.T.A.R. programming element he stole. Both heroes are beaten and brought aboard the satellite by Lex and Doc Ock. Luthor reveals he wants to set off a chain reaction weather system as a way to extort 10 billion dollars from the U.S. government. After a brawl between the four, Superman leaves to battle the tidal wave created by Luthor while Spider-Man remains on the satellite to fight the two villains. After Ock understands Luthor's plan will destroy the planet he destroys a control panel. With his use of superspeed, Superman is able to counter the energy of the tidal wave and prevents it from destroying the coastline. Each hero carries off his villain to a prison.
In an epilogue, Clark and Lois go on a double-date with Peter and Mary Jane, and they all walk away together.
- This one-shot was the first ever crossover between DC Comics and Marvel Comics.