Gotham City-based vigilante Batman travels to Metropolis to preemptively combat Superman, fearing what would happen if the latter is kept unchecked, while another threat endangers humankind.
The planet Krypton faces imminent destruction due to its unstable core; the result of depleting Krypton's natural resources. The ruling council is deposed by the planet's military commander, General Zod, and his followers during a coup d'état. Knowing that artificial population control and isolationism have ruined their civilization, scientist Jor-El and his wife Lara launch their newborn son, Kal-El, the first naturally born Kryptonian child in centuries, on a spacecraft to Earth after infusing his cells with a genetic codex of the entire Kryptonian race. After Zod kills Jor-El, he and his followers are captured and exiled to the Phantom Zone. However, they are indirectly freed after Krypton explodes, rendering the Kryptonian race extinct apart from Zod and his forces.
Alimenté par sa foi restaurée en l’humanité et inspiré par le sacrifice de Superman, Batman constate l'arrivée d'éclaireurs extraterrestres — appelés "Paradémons" et attirés par la peur de leurs victimes — et comprend que l'attaque majeure prophétisée par Lex Luthor (dans le film Batman v Superman : L'Aube de la justice) est imminente, or Superman est mort et ne peut plus protéger l'humanité. Conscient de ses propres limites, il contacte Diana Prince/Wonder Woman et tente de former avec elle une ligue de super-héros. Il part retrouver Arthur Curry, dit Aquaman, qui habite à Atlantis, tandis que Diana va approcher Victor Stone, footballeur devenu à moitié machine après un accident et capable d'influer sur les technologies, mais les deux hommes refusent de les aider. Barry Allen, jeune homme doté de super-vitesse, accepte avec enthousiasme l'offre de Bruce Wayne.
Bruce Wayne and Lex Luthor are both nominated for the Man of the Year award, and Wayne wins. As he is making his speech, the Joker breaks in with the Riddler, Harley Quinn, the Penguin, Two-Face, Poison Ivy, Bane, Catwoman, and steals the award, as well as money and gems. Batman arrives and stops everyone except the Joker, who escapes on his boat, but Robin's helicopter picks up Batman. When the rope holding Batman is broken, he calls in the Batwing and defeats the Joker. Meanwhile, Luthor is running for president, but his poll figures are terrible. He learns that the Joker knows how to produce more Kryptonite, and can make a gas that makes people love him, which will help Luthor win the election and defeat Superman. He breaks the Joker out of Arkham Asylum and promises him the use of Luthor's De-Constructor weapon to defeat Batman by dismantling all his gadgets and vehicles.
In the Lego universe, the wizard Vitruvius attempts to protect a superweapon called the "Kragle" from the evil Lord Business. He fails to do so, but prophesies that a person called "the Special" will find the Piece of Resistance capable of stopping the Kragle.
Superman (Brandon Routh) has been missing for five years, since traveling to the location where astronomers believed they had discovered the remains of Krypton. During his absence, Superman's nemesis, mad scientist Lex Luthor (Kevin Spacey), was released from prison (due to Superman's failure to appear at Lex's trial) and married an old rich widow (Noel Neill) to obtain her fortune upon her death. Having failed in his quest to find surviving Kryptonians, Superman returns to Earth and, as Clark Kent, resumes his job at the Daily Planet in Metropolis. He subsequently learns that Lois Lane (Kate Bosworth) has won a Pulitzer Prize for her article "Why the World Doesn't Need Superman". Meanwhile, Lex travels to the Fortress of Solitude and steals Kryptonian crystals to use for an experiment that causes a mass power outage on the East Coast. The power loss interferes with the flight test of a space shuttle to be launched into space from its piggy-back mounting on an airliner, occupied by Lois Lane, who is covering the story. Clark flies into action as Superman and stops the plane from crashing onto a baseball stadium.
On the planet Krypton, using evidence provided by scientist Jor-El, the Ruling Council sentences three attempted insurrectionists, General Zod, Ursa, and Non, to "eternal living death" in the Phantom Zone. Despite his eminence, Jor-El is unable to convince the Council of his belief that Krypton will soon be destroyed when its sun explodes. To save his infant son, Kal-El, Jor-El launches a spacecraft containing him toward Earth, a distant planet with a suitable atmosphere, and where Kal-El's dense molecular structure will give him superhuman powers. Shortly after the launch, Krypton is destroyed.
Prior to the destruction of Krypton, the criminals General Zod (Terence Stamp), Ursa (Sarah Douglas) and Non (Jack O'Halloran) are sentenced to banishment into the Phantom Zone for insurrection and murder, amongst other crimes.
Gus Gorman, a chronically unemployed loser, discovers he has a talent for computer programming and gets a job at the Metropolis-based conglomerate Webscoe. Gus, dissatisfied with his pay, embezzles from his employer using a technique known as salami slicing, which brings Gus to the attention of CEO Ross Webster. Webster is intrigued by the computer's potential to aid him in his schemes to rule the world financially. Joined by his sister Vera and his "psychic nutritionist," Lorelei Ambrosia, Webster blackmails Gus into helping him.
Superman saves a spaceship of cosmonauts whose ship was thrown off course by debris, then visits his home-town of Smallville as Clark. Now that his adoptive parents have died, Clark has inherited their now-unattended farm. In an empty barn, he uncovers the capsule that brought him to Earth, and removes a luminescent green Kryptonian energy module. A recording left by his mother Lara (voiced by Susannah York) states that its power can be used only once. Unwilling to sell the farm to a mall developer, Superman returns to Metropolis.
In June 1959, Louis Simo (Adrien Brody), a Los Angeles private investigator more interested in generating an income than in devotion to his clients, is spying on the wife of a man named Chester Sinclair to find if she is cheating. On a visit to his own ex-wife Laurie, Simo learns that his son is upset over the recent death of actor George Reeves, who played Superman on television. Reeves was found dead inside his Beverly Hills home with a gunshot wound to the head, which police ruled a suicide.
Kara Zor-El (Helen Slater) lives in an isolated Kryptonian community called Argo City, in a pocket of trans-dimensional space. A man named Zaltar (Peter O'Toole) allows Kara to see a unique an immensely powerful item known as the Omegahedron, which he has borrowed without the knowledge of the city government, and which powers the city. However, after a mishap, the Omegahedron is blown out into space. Much to the distress of her parents (Simon Ward and Mia Farrow), Kara follows it to Earth (undergoing a transformation into "Supergirl" in the process) in an effort to recover it and save the city.
LexCorp's CEO, Lex Luthor, has been elected President of United States during a severe nationwide economic depression. Under his leadership, the economy begins to thrive, and he assembles a force of government-employed superheroes consisting of Captain Atom, Katana, Black Lightning, Power Girl, Starfire, and Major Force. Meanwhile, Superman and Batman maintain their distrust toward Luthor.
The film opens with a narration by Lex Luthor (James Marsters), highlighted by images of Superman doing heroic deeds. Lex describes Superman as a god on Earth, but insists that "there comes a time when even gods must die."
In an alternate universe where evil usually triumphs over good and where the roles of the heroes and villains are reversed from their counterparts in the mainstream DC Universe, heroic analogues of Lex Luthor and the Joker (called the Jester) are attempting to steal a device, the "Quantum Trigger", from the headquarters of the Crime Syndicate. The pair trip an alarm but manage to secure the device. The Jester sacrifices himself to allow Luthor to escape and kills J'edd J'arkus and Angelique (alternate versions of Martian Manhunter and Hawkgirl respectively) with a radioactive bomb. Luthor is confronted by the remaining Syndicate members (Ultraman, Superwoman, Power Ring, Johnny Quick and Owlman) but escapes to the Earth of the heroic Justice League by activating a dimensional travel device.