While locked up in the Slab penitentiary, the Joker finds he has a terminal brain tumor. Determined to go out with a bang, he uses a venom to "jokerize" other inmates, making them insane and bear a physical resemblance to his own white skin, green hair, and wide smile. A riot breaks out in the Slab and Black Canary, Nightwing, and Batman move in to put it down while Dina Bell and Shilo Norman are trapped inside. The Joker prompts Black Mass to suck the prison into a black hole while he and the other villains escape. Blue Beetle narrowly rescues Black Canary, Batman, and Nightwing while Dina and Shilo are not as lucky. Barbara Gordon feels remorseful for being absent on a date with Dick Grayson (Nightwing) while the riot first broke out and begins to wish she could kill the Joker for the pain he's caused in her life.
Chaos soon spreads throughout the entire DC Universe and war is declared against the Joker by President Lex Luthor. While JLA searches for him, the Joker hides out on Easter Island and sends his minions to capture Harley Quinn so he can impregnate her and produce an heir. Harley is eventually rescued by Spoiler, Batgirl, and Power Girl. Harley is upset that the Joker had tried to do this without marrying her first.
Meanwhile, the Joker grows disgruntled at the lack of creativity behind his minions' havoc, realizing that "every other crisis" involves red skies and crazy weather. With the assistance of Stormfront and Mr. 104, the Joker poisons the atmosphere and creates "crazy rain", spreading his laughing toxin across the world. His next plan is the assassination of President Luthor.
While the "jokerized" villains are being rounded up, Kirk Langstrom discovers that the venom they are affected with is also deadly and works to produce an antidote with the reluctant help of Harley Quinn. Black Canary also discovers that the Joker's CAT scans were modified and that doctors lied to him about his death with the hope that it would cause him to lead a more sane life.
Inside the Slab, Shilo and Dina are struggling to find a way to get themselves and the prison back to earth. They initially try to find Black Mass to reverse the gravity well with the help of Mister Mind, however Dina accidentally shoots Black Mass during a run-in with the Maneaters. They eventually resort to killing Multi-Man over and over until he is able to reanimate Black Mass who then sends them back to earth.
Huntress is sent to Arkham Asylum to find Robin, who disappeared into the building and stopped sending out reports. After encountering Killer Croc, she finds what appears to be Robin's remains. Nightwing, enraged over Robin's death, goes to face the Joker one-on-one and beats him to near-death until the Bat family, Robin included, arrives on the scene much to Nightwing's surprise. The Joker is revived and returned to prison where he is put in a windowless, doorless cell (with out an audience to entertain. The jokerized villains are finally returned to their normal selves and all is well, until the next crisis that is.