Mark Harmon,Gina Torres,Kari Wuhrer,James Woods
The movie begins in an alternate universe where Lex Luthor and a heroic analogue to the Joker named the Jester are stealing a device from Crime Syndicate headquarters. After securing the "Quantum Trigger," Luthor and the Jester attempt to escape, but an alarm makes them realise the Syndicate are approaching. The Jester sacrifices himself with a bomb to allow Luthor a chance to get away, killing J'edd J'arkus (the Martian Manhunter's opposite) and Angelique (Hawkgirl's counterpart) who has just stabbed him with her flaming sword, in the process. Lex Luthor is confronted by the remaining Syndicate members, only to activate his dimensional travel device and escape to the Earth of the heroic Justice League, they are delayed thinking his device is a weapon.
Once there, he turns himself over to the police, who he knows will think he's the evil Luthor from this world and thereby summon the Justice League. Superman's x-ray vision confirms Lex Luthor's reversed organs mean that he's from a parallel Earth, and that "their" Lex Luthor is still in the Stryker's Island prison, so the League agrees to hear Lex out. Lex tells his story and asks the League for help: his Earth is being extorted by the Syndicate, who have taken control of all of Earth and systematically eliminated Luthor's Justice League members. The only thing holding them in check is the threat of a nuclear response. While waiting outside the League's meeting room, he hides the Quantum Trigger. All members of the League agree, except for Batman, who argues that the League is spread too thin for the problems of their own world, let alone Luthor's. Luthor transports the remaining members of the League to his universe, while Batman stays behind to finish building the Watchtower.
Arriving at Justice League headquarters on Lex's parallel Earth, they find the Syndicate and must soon retreat. Regrouping at Jester's base, they make plans to attack Syndicate targets, and they even capture Ultraman, the villainous counterpart to Superman. However, United States President Slade Wilson orders his release, to the outrage of Lex and the Justice League. Wilson explains that he didn't "roll over" for the Syndicate, and that acceding to the Syndicate's demands saves millions of lives. His daughter, Rose, regards him as a coward. J'onn J'onzz inadvertently reads her mind and explains that Wilson isn't, that as a military man he actually holds life more dear than others. J'onn later saves Rose's life during an assassination attempt, and they start to fall in love.
Owlman, Batman's counterpart, is building a weapon, the Quantum Eigenstate Device or Q.E.D., which the Syndicate intends to use as the equalizer to the nuclear threat. When pressed by Superwoman, Wonder Woman's counterpart, with whom he appears to be in a relationship, Owlman admits the weapon can destroy entire worlds. Operating under the theory that there are many parallel Earths, and that each one develops from the choices that every single person makes, Owlman becomes obsessed with the idea that nothing he does can possibly matter, as there will always be parallel worlds where he explored another option. Owlman begins fervently seeking Earth-Prime, the very first Earth from which all other universes branched off. Owlman plans to use his weapon to destroy Earth-Prime, causing a chain reaction that would erase the entire multiverse, as it is the only action that would not result in the creation of another alternate universe where a different choice was made; in his opinion, the only choice that could "matter". Superwoman notes that even as a "murdering psychopath," she thinks Owlman is much crazier than she is, but agrees to help him because it would allow her to kill everyone who ever existed. When the League eventually arrives at the moonbase of the Crime Syndicate, it becomes a free-for-all fight as everyone is matched up against their alternates and, in some cases, have to help each other gain the upper hand. Eager to put his plan into action, Owlman activates the Q.E.D., and takes it to Earth-Prime. Batman deduces which universe holds Earth Prime, but without a way to get there, it appears that everyone is doomed. A plan is hatched in which Johnny Quick (the Flash's counterpart) uses his speed to eventually match the temporal vibration with the vibration of his own molecules, opening another portal to Earth-Prime so that Batman can engage Owlman.
Owlman and Batman are mental equals, but Owlman is shown to be superior in combat. However, Batman outwits Owlman at the last moment, sending him and the Q.E.D. to an uninhabited Earth just before the bomb detonates. Owlman has the opportunity to disarm it in the last seconds, but in the end does nothing and dies in the ensuing blast, saying, "It doesn't matter."
Back on the Crime Syndicate's world, Johnny Quick dies after the vibrating caused him to age rapidly. Batman had anticipated that, which is the real motive behind claiming Flash was too slow to open the portal. The remaining members of the Syndicate (Ultraman, Superwoman, and Green Lantern counterpart Power Ring) are arrested by the U.S. Marines, led personally by President Wilson after J'onn.
Wilson thanks the Justice League for giving them back their world and they are sent back to their own dimension. When they return, Wonder Woman keeps the still-cloaked plane that she stole from Owlman. Because of the League's forces being spread too thin, Batman thinks about a membership drive and opens the door to the heroes (Aquaman, Red Tornado, Black Lightning, Firestorm, and Black Canary) that he had summoned for help earlier and keeps them around to start expanding the League.