The film begins with an introductory sequence involving the main characters and images from space, set to the prelude of Richard Wagner's Tristan und Isolde. These sixteen slow motion shots symbolically reveal key elements of the film: Justine in deep melancholy with birds falling behind her; the estate lawn and a sundial with everything casting two shadows; Pieter Brueghel's The Hunters in the Snow burning; Melancholia covering Antares; Claire carrying Leo through the golf course as her feet sink into the ground; a black horse collapsing under an aurora; Justine standing among clouds of insects emerging from the ground; Justine, Leo and Claire under a sky with Melancholia, the Moon and the Sun visible; Melancholia passing by Earth; electric currents coming off of utility poles and Justine’s fingers; Justine in her wedding attire trudging through a dark stringy material; Melancholia coming back towards Earth; a burning tree outside of a window; an unconscious or dead Justine, again in her wedding attire, floating in water; Leo looking at the sky in shock as he and Justine gather and shave branches in the forest; and lastly Earth colliding with Melancholia.
Part One: "Justine"
Delayed by their stretch limousine's difficulty traversing the narrow winding rural road, newlyweds Justine and Michael arrive two hours late for their own wedding reception at the estate of Justine's sister, Claire, and her husband, John. Upon their arrival, Justine takes note of a brightly shining red star in the sky. John explains it is the star Antares, in the constellation Scorpius.
Justine has a dysfunctional family: brother-in-law John constantly complains about having to pay for the wedding despite being very well-off; father Dexter is hedonistic and selfish to the point of narcissism, while mother Gaby is brutally jaded, openly declaring her hatred of marriages during her wedding speech. No one ever asks what Justine wants, or why she is unhappy, but throughout the dinner she is praised for being beautiful.
Claire urges Justine to hide her debilitating melancholy from her new husband Michael. Justine finds several excuses to flee the wedding reception and wander the estate by herself. At one point, while the guests stand around waiting for the cutting of the cake, Justine and Gaby independently escape to take baths. Michael is pressured to give a speech at one point, but it is very dispassionate and vapid. He attempts to consummate his marriage with Justine, despite her being clearly non-receptive, even ignoring her at one point when she asks if they can simply sit together for a while, causing her to flee in frustration. Claire tells Justine she is "lying to everyone", while John aggressively reminds Justine how much the wedding cost and tells her she "better be God damn happy".
Justine's boss, Jack, is ruthless and greedy. During his wedding speech, he's hustling Justine to meet a work deadline. He pushes her throughout the evening to create a tagline to promote a new campaign. Her boss's nephew, Tim, is given the chance to exploit the opportunity to get the tagline at all costs in order to promote his career: a task similar to what Justine was previously so successful at. He reluctantly, but doggedly, pursues Justine throughout the wedding reception, pressuring her for the tagline.
Eventually, Justine goes out onto a sand trap and has sex with Tim. Unable to get the tagline from Justine, Tim is later fired for his "professional" failure. Finally reaching a breaking point, Justine resigns by telling Jack that he is a "despicable, power-hungry little man", and storming off. After several hours of being alienated from each other, Justine and Michael quietly agree to call off the marriage. Michael departs, leaving a severely depressed Justine isolated at the estate, with Claire and John furious at her. While storming back into the estate, a wedding planner tells Claire the total number of beans in a jar for a lottery that was held during the event.
Early the following morning, while horseback riding with Claire, Justine notices Antares is no longer visible in the sky.
Part Two: "Claire"
Later, the reason for Antares's disappearance has become public knowledge: a newly discovered rogue planet called Melancholia, which entered the Solar System from a point behind the Sun, was blocking the star from view. The planet has now become visible in the sky as it approaches ever closer to Earth. John is excited about the "fly-by" predicted by scientists, while Claire is frightened by alternate predictions of Earth being hit and destroyed.
In the meantime, Justine's depression has grown worse. She can barely muster the mental strength to get inside a cab to arrive to Claire's and John's estate, and is essentially catatonic upon arrival. Claire takes her sister under her care. One day, while horseback riding, Justine finally notices Melancholia in the sky, visible to the naked eye.
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