Thousands of years ago, Steppenwolf and his legions of Parademons had attempted to take over the Earth using the combined energies of the three Mother Boxes. The attempt was foiled by a unified alliance including the Olympian Gods, Amazons, Atlanteans, humanity, and extraterrestrial beings. After Steppenwolf's army was repelled, the Mother Boxes were separated and hidden in different locations. In the present, humanity is still in mourning two years after Superman's death, which triggered the Mother Boxes' reactivation and Steppenwolf's return to Earth. Steppenwolf aims to regain favor with his master Darkseid by gathering the boxes to form "The Unity", which will destroy Earth's ecology and terraform it in the image of Steppenwolf's homeworld.

Steppenwolf retrieves one Mother Box from Themyscira, prompting Queen Hippolyta to warn her daughter Diana. Diana joins Bruce Wayne in an attempt to unite other metahumans to their cause: Wayne goes after Arthur Curry and Barry Allen, while Diana locates Victor Stone. Wayne fails to persuade Curry but finds Allen enthusiastic to join the team. Although Diana fails to persuade Stone to join, he agrees to help them locate the threat. Stone later joins after his father Silas and several other S.T.A.R. Labs employees are kidnapped by Steppenwolf, who is seeking the Mother Box protected by humanity.

Steppenwolf attacks an Atlantean outpost to retrieve the next Mother Box, forcing Curry into action. The team receives intel from Commissioner James Gordon, leading them to Steppenwolf's army in an abandoned facility under Gotham Harbor. Although the group rescues the kidnapped employees, the facility is flooded during combat, which traps the team until Curry helps delay the flood so they can escape. Stone retrieves the last Mother Box, which he had hidden, for the group to analyze. Stone reveals that his father used the Mother Box to rebuild Stone's body after an accident almost cost him his life. Wayne decides to use the Mother Box to resurrect Superman, not only to help them fight off Steppenwolf's invasion but also to restore hope to humanity. Diana and Curry are hesitant about the idea, but Wayne promises a secret contingency plan in case Superman returns as a hostile.

Clark Kent's body is exhumed by Cyborg and placed in the amniotic fluid of the genesis chamber in the Kryptonian scout ship, along with the Mother Box which Flash activates, successfully resurrecting Superman. However, Superman's memories have not returned, and he attacks the group after Stone accidentally launches an attack at him. On the verge of being killed, Batman enacts his contingency plan: Lois Lane. Superman calms down and leaves with Lane to his family home in Smallville, where he reflects, and his memories slowly come back. In the turmoil, the last Mother Box is left unguarded, allowing Steppenwolf to retrieve it. Without Superman to aid them, the five heroes travel to a village in Russia where Steppenwolf aims to unite the Mother Boxes once again to remake Earth. The team fights their way through the Parademons to reach Steppenwolf, but are unable to distract him enough for Stone to separate the Mother Boxes. Superman arrives and assists Allen in evacuating the city, as well as Stone in separating the Mother Boxes. The team defeats Steppenwolf, who, overcome with fear, is attacked by his own Parademons before they all teleport away.

After the battle, Bruce and Diana agree to set up a base of operations for the team, with room for more members. As the team establishes, Diana steps back into the public spotlight as a heroine; Barry acquires a job in Central City's police department, impressing his father; Victor continues to explore and enhance his abilities with his father in S.T.A.R. Labs; Arthur embraces his Atlantean heritage and continues protecting people on the seas; Superman resumes his life as reporter Clark Kent and as protector of Earth; and Bruce gets the Kents' house back from the bank. In a post-credits scene, Lex Luthor has escaped from Arkham Asylum and recruits Slade Wilson to form their own league.
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