Avec la mort de Superman, Amanda Waller, qui dirige le programme ARGUS, craint l'apparition du prochain méta-humain qui pourrait attaquer l'humanité. Pour prévenir cette possibilité, elle fait adopter le projet Task Force X (Force Spéciale X), visant à utiliser une équipe de criminels aux capacités hors normes pour répondre aux menaces, mais de façon non officielle. Elle a déjà plusieurs noms sur sa liste, comme le tireur d'élite Floyd Lawton / « Deadshot », capturé par Batman en lui rappelant la vie qu'il fait mener à sa fille Zoe, la psychopathe Harley Quinn, ancienne psychiatre de l'asile d'Arkham tombée sous le charme du Joker, arrêtée par Batman alors qu'elle était coincée dans une voiture qui coulait dans une rivière, le tueur monstrueux Waylon Jones, surnommé « Killer Croc », Digger Harkness, un voleur australien capturé par Flash alors qu'il dérobait des diamants et El Diablo, un gangster mexicain doué de pyrotechnie qui s'est rendu lui-même après avoir involontairement brûlé sa femme et ses enfants. Amanda Waller a déjà recruté le Colonel Rick Flag, soldat émérite. Lorsqu'elle présente le projet au Général Edwards, elle lui montre aussi les pouvoirs de l'Enchanteresse, un être mystique qui habite dans le corps de l'archéologue June Moon. Amanda Waller arrive à la contrôler car elle détient le cœur de la sorcière, et elle s'est arrangée pour faire en sorte que Rick Flag et June Moon deviennent amants afin de manipuler le soldat.
Barbara Gordon traque les criminels de Gotham City dans le costume de Batgirl. Une nuit, elle tente d'arrêter des braqueurs seule mais échoue ; Batman intervient et capture l'un des voleurs en fuite. Les deux justiciers identifient l'organisateur : Paris Franz, neveu du parrain du crime Lord Francesco, qu'il souhaite évincer pour prendre sa place, et qui commence à être obsédée par Batgirl. Batman demande à sa protégée de le laisser faire mais elle refuse. Quand Franz piège Batgirl en la menant vers le cadavre de Francesco, Batman lui interdit de s'impliquer dans l'affaire. Furieuse, Batgirl commence à frapper Batman et le plaque au sol avant de l'embrasser, puis ils couchent ensemble. La nuit sème la confusion dans la relation entre Batman et Batgirl. Franz se manifeste à nouveau, piégeant Batman, et Batgirl intervient mais manque de le tuer. Barbara se rend compte que Batman avait raison et abandonne son costume.
Batman doit faire face au plus grand défi de sa vie : les vacances ! Le chevalier noir accepte à contre-coeur de laisser Batgirl et Nightwing l'emmener pour un repos longtemps repoussé loin de la lutte contre le crime, laissant Gotham City sous la protection de Superman et de la Ligue des Justiciers. Rien ne se déroule comme prévu lorsque les vacances de Batman sont écourtées par des dangers provenant de son passé et des envahisseurs du centre de la Terre. Superman et les autres membres de la Ligue des Justiciers réalisent très vite la quantité de travail qu'a Batman dans sa lutte quotidienne contre le crime à Gotham.
When Gotham is plagued by crime committed by an animal-themed villain squad composed of The Penguin, Silverback, Cheetah, Killer Croc and Man-Bat, Batman and other heroes band together to stop them.
Crime is on the run as the newly formed Justice League keeps Metropolis safe and this makes evil genius Lex Luthor very unhappy. Together with Black Manta, Sinestro and a gang of ruthless recruits, Lex builds his own league and declares them the Legion of Doom.
In the Eastern European country of Sokovia, the Avengers – Tony Stark, Steve Rogers, Thor, Bruce Banner (Hulk), Natasha Romanoff, and Clint Barton – raid a Hydra outpost led by Baron Wolfgang von Strucker, who has been experimenting on humans using the scepter previously wielded by Loki. They encounter two of Strucker's experiments – twins Pietro, who has superhuman speed, and Wanda Maximoff, who can manipulate minds and project energy – and apprehend Strucker, while Stark retrieves Loki's scepter.
In 1989, scientist Hank Pym resigns from S.H.I.E.L.D. after discovering their attempt to replicate his Ant-Man shrinking technology. Believing the technology is dangerous, Pym vows to hide it as long as he lives. In the present day, Pym's estranged daughter, Hope van Dyne, and former protégé, Darren Cross, have forced him out of his own company. Cross is close to perfecting a shrinking suit of his own, the Yellowjacket, which horrifies Pym.
Friends Reed Richards (Miles Teller) and Ben Grimm (Jamie Bell) have worked together on a prototype teleporter since childhood, eventually attracting the attention of Professor Franklin Storm (Reg E. Cathey), director of the Baxter Foundation, a government-sponsored research institute for young prodigies. Reed is recruited to join them and aid Storm's children, scientist Sue Storm (Kate Mara) and the somewhat reckless technician Johnny Storm (Michael B. Jordan), into completing a "Quantum Gate" designed by Storm's wayward protégé, Victor von Doom (Toby Kebbell), who begrudgingly agrees to help due to his unrequited feelings for Sue.
In the Atlantic Ocean, the USS California submarine picks up incoming human-like threats approaching the sub by sonar. The sub is attacked, leaving the entire crew dead by the invading hostiles. At S.T.A.R. Labs' Justice League headquarters, Cyborg is given news by Colonel Steve Trevor over the sunken sub. Cyborg decides to check it himself, deciding against Trevor's idea of calling the other superheroes, as he puts it "there is no Justice League".
During an investigation of missing children, Damian Wayne, still fighting crime as Robin, has taken the Batmobile out to an abandoned toy factory without Batman's consent, where he finds Anton Schott, who is responsible for the children's disappearance and has also transformed some of them into grotesque, mutilated "Dolls". Damian's father, Bruce, arrives as Batman to aid Damian in the resulting battle, with Damian chasing after the Schott while Batman knocks out the Dolls with gas and frees the remaining children. Damian chooses to spare Schott, only for an owl-masked assassin to kill him, telling Damian to never doubt his instincts. The assassin leaves Damian and the Schott's body behind, leading Batman to accuse Damian of murdering him when he arrives. Damian insists he spared Schott out of respect for Batman, and after inspecting the body further, Batman discovers an owl feather.
In an alternate universe, the Justice League is a brutal force that maintains order on Earth. This universe has its own versions of Superman, Batman, and Wonder Woman:
It’s Halloween night in Gotham City and Scarecrow, Clayface, Silver Banshee and Solomon Grundy have hit the streets to stir up trouble! Batman is on the trail of the city’s spookiest villains while, further complicating matters, the clown prince of crime himself, The Joker, is ruling over this mysterious crew of misfit criminals. It’s up to the Dark Knight to stop this gruesome gang before they unleash “digital laughter,” a computer virus that’s part of a diabolical plan to jeopardize all of Gotham City’s vital technology. Batman, Green Arrow, Cyborg, Nightwing and Red Robin must combine forces to battle these baddies and save the city.
OsCorp scientist Richard Parker records a video message to explain his disappearance. Later, he and his wife, Mary, are aboard a private jet hijacked by a man sent to assassinate Richard. The plane crashes, killing both Richard and Mary, after he uploads the video.
In 1988, following his mother's death, a young Peter Quill is abducted from Earth by the Ravagers, a group of space pirates led by Yondu Udonta. Twenty-six years later on the planet Morag, Quill steals an orb, after which Korath, a subordinate to the fanatical Kree, Ronan, intercepts him. Although Quill escapes with the orb, Yondu discovers his theft and issues a bounty for his capture, while Ronan sends the assassin Gamora after the orb.
In the future, robots known as Sentinels are exterminating mutants and their human allies. A band of mutants, including Kitty Pryde, Colossus, Iceman, Bishop, Warpath, Blink and Sunspot, evade the Sentinels due to Pryde's ability to send a person's consciousness to the past. Pryde's group convenes with Logan, Storm, Professor Charles Xavier, and Erik Lehnsherr at a monastery in China. Pryde sends Logan's consciousness 50 years back in time to 1973 to prevent Mystique from assassinating Dr. Bolivar Trask, creator of the Sentinels. Following the assassination, Mystique was captured, and her DNA was used by Trask's company to improve the Sentinels, whose ability to adapt to any mutant power makes them almost invincible. Xavier and Lehnsherr advise Logan to find both of their younger selves for help.