NOTE: This spoiler was submitted by Jeremy

The film starts in May 2020, in the early days of the COVID-19 pandemic. Connecticut Governor Claire Debella (Kathryn Hahn) is conducting an at-home interview when she receives a mysterious package. At Alpha Industries, scientist Lionel Toussaint (Leslie Odom Jr) is in a video call with his higher-ups, who are begging him not to sign off on the insane ideas of his boss, Miles Bron (Edward Norton), as he is set to potentially put lives at risk with his latest creation. Lionel is then sent the same package from Miles.

At a party, supermodel Birdie Jay (Kate Hudson) is being taken care of by her put-upon assistant Peg (Jessica Henwick), as they receive the package from Miles as well, and Peg is trying to keep a drunken Birdie away from her phone. Finally, mens rights Twitch star Duke Cody (Dave Bautista) is making a video with his girlfriend Whiskey (Madelyn Cline) when his mother (Jackie Hoffman) tells him he got the package too. Claire, Lionel, Birdie, and Duke all hop on a phone call to try and figure out how to open the box. After Lionel figures it out, the rest of the box is a series of puzzles that lead to a model of a building and an invitation from Miles to his private island for the weekend. The last person to receive the package is Cassandra “Andi” Brand (Janelle Monae), who simply smashes the box to pieces before finding the invitation.

Detective Benoit Blanc (Daniel Craig) is in a bathtub on a video chat with Natasha Lyonne, Angela Lansbury, Stephen Sondheim, and Kareem Abdul-Jabbar, all of whom express concern for Blanc not leaving his apartment in between cases. Blanc’s partner Philip (Hugh Grant) then calls Blanc to inform him that he has received a box.

Blanc later joins the guests as they arrive at a dock for a ship that will take them to Miles’s island. Claire, Birdie (joined by Peg), Lionel, and Duke (joined by Whiskey) express enthusiasm at meeting Blanc for his famous cases. Just before they depart, they are instructed by Miles’s assistant (Ethan Hawke) to take in a disinfectant that will allow them to interact without using masks. As they get on the boat, everybody is stunned to see Andi arriving. On the ship, Blanc is told by Lionel that everyone is surprised that Andi is there since she had a rather infamous falling out with Miles when he cut her out of a major business deal.

The guests arrive on Miles’s island, where he arrives to greet them, along with a random guest he has named Derol (Noah Segan). Miles then shows off his home, the Glass Onion, which is named after a bar that the group used to hang out at. He announces that they will be partaking in a murder mystery where he is the victim, and he gives them all special bracelets to their rooms, and Blanc appears to meet Andi for the first time. Blanc then goes to Miles’s office, as it turns out that Miles did not actually invite Blanc to the gathering, but he still received the invitation.

The guests get settled in and go for the pool, drinking spiked kombuchas. During this time, Whiskey appears to be getting close to Miles, even with Duke noticing. Peg approaches Birdie and tells her to talk to Miles about a personal matter, and Birdie comments on how Miles was a nobody when she met him. Miles sits down to give a little speech to the group before Andi comes over to rail against him and the others, since she knows that they are latching onto Miles because he backs all their ventures (Claire’s run in politics, Duke’s Twitch career, etc.).

Peg then goes to find Miles and asks him herself to lay off of Birdie, as the matter concerns a sweatshop in Bangladesh that made the clothes she manufactures, but Miles isn’t backing down. Blanc attempts to smoke a cigar but is scared off by an alarm. He then sees Duke catching Miles and Whiskey hooking up in his bedroom.

At night, Miles gathers people around for drinks before sitting down for the mystery. Just as the mystery begins, Blanc almost immediately deduces that the would-be murderer is Birdie, as she is seated directly across from a statue that has a time-released crossbow that would strike Miles. Sure enough, the arrow “kills” Miles, which annoys him but impresses everyone else. Miles goes to clean himself up, with Blanc following him and apologizing for ruining the surprise so soon, although he makes it clear that he has brought people together who all have actual motives to want him dead. Blanc then notices an artifact that Miles has framed, which is a cocktail napkin where he supposedly wrote the details that led to Alpha’s development.

While the guests continue drinking, Miles points out that he has the actual Mona Lisa on loan from the Louvre since they need money due to the pandemic. It has a sensitive alarm system with a failsafe out in the open. Miles then gathers everyone for another presentation. He has developed a new, untested fuel source called Klear, which the entire Glass Onion is powered by. Lionel tells him this is crazy because he needed at least two years to test Klear before it could be unveiled to the public. Andi calls Miles out again, and she is confronted by Duke, who tells her that she simply lost in the long run. She walks away from the party.

Everyone continues to party, and Duke brings Miles’s attention to something on his phone, which says could be a game-changer and would score Duke a coveted spot in Alpha News. Miles fixes a drink and passes it to Duke, who begins choking moments later. The others attempt to help, but Duke dies. The group starts to look for his phone, but nobody can find it since it has stopped beeping from notifications. People begin to suspect that Miles was the target and that someone meant to poison him, and they also notice that the gun that Duke always has on his person is missing.

When the clock strikes 10, the lights all around the place begin to go out. Whiskey comes in yelling that Andi ransacked their room. Blanc goes after Andi in the darkness, but just as they begin talking, an unseen assailant fires a gun, hitting Andi. The rest of the group comes out and sees Blanc standing over her. He then gathers the group in another room.

The film then jumps back to when Blanc received the invitation. He was visited by Helen, Andi’s twin sister, who brought him the smashed-up puzzle box. Helen tells Blanc that Andi is said to have committed suicide days earlier, but she believes that Andi was murdered. Miles had cut Andi out of the Klear deal because she knew it was potentially dangerous, but he went behind her back and got Claire, Lionel, Duke, and Birdie to testify against Andi to completely cut her out of Alpha. Helen points out that the four of them were all originally close friends with Andi and that it was her who introduced them to Miles, whom they all considered to be a loser. Only when he made it to the top and helped them out did they suddenly care for him. In Andi’s rage, she came across the REAL cocktail napkin, where she came up with all the Alpha ideas that Miles stole and passed off as his own. Helen thinks one of the group poisoned Andi and left her body in her car to make it look like a suicide, as the envelope was missing from her home and there was no suicide note.

Blanc comes up with the idea that he and Helen go to the island with Helen posing as Andi. Despite her initial objections, she can change her hair and accent to pass herself off as Andi. On the boat, Duke and Birdie express surprise for “Andi’s” appearance, so Blanc coaches Helen on how to avoid suspicion. When they are on the island, Helen gets drunk and snoops on the guests to gather motives and opportunities. She overhears Lionel and Claire talking about how their careers are in trouble with Klear, as Claire could lose potential voters for backing it, and Lionel hasn’t made it disclosed that Klear would be susceptible to leakage, which could cause massive explosions. Helen also drops a recorder in Birdie’s bag, which captures her conversation with Peg, where Birdie admits to signing off on a statement where she would take full responsibility for the Bangladesh sweatshops so Miles could compensate her. Finally, Helen speaks to Whiskey and learns that she is not comfortable in her relationship with Duke, who just sees her as arm candy. It also turns out that he asked Whiskey to seduce Miles to convince him to let Duke on Alpha News, but Miles doesn’t want the bad press since Duke tried to market erection pills to teenage boys.

During the evening party, Blanc tells Helen to initiate the argument that she would lose, so she can have an excuse to leave the party and go through peoples rooms to look for the envelope. After Duke is killed, Whiskey catches Helen in her room and aims a trident gun at her, but the lights going out gives Helen an opportunity to run. She and Blanc catch up to each other before the assailant shoots at her. Helen survives since she had one of Andi’s handbooks on her person, but Blanc uses Jeremy Renner brand hot sauce to make it look like Helen is dead to the rest of the group, which gives her an opportunity to continue her search.

Helen finds the envelope in Miles’s office, and she starts to receive condolences from people over Andi’s death, as it has just been made public news. At that moment, Blanc tells the group that Miles is not the tech genius that he paints himself as, due to his use of malapropisms and other boneheaded ideas. He goes further and tells them outright that Miles is the real killer. Despite him telling people that Duke mistakenly grabbed the glass meant for Miles, he directly handed it to him and also took his gun, where he waited for an opportunity to plant the gun and let the lights go out, which Blanc indirectly gave him the idea to do. The reason for Duke’s death was because he showed Miles the article on Andi’s death, which he figured he could use to blackmail him with to get him into Alpha News. Miles put pineapple juice in Duke’s drink, knowing he was deathly allergic to pineapples. Days earlier, Duke was almost hit by Miles’s car as he was seen leaving Andi’s place. Duke, Claire, Lionel, and Birdie all went to check on Andi but found no answer. Miles had killed her because he caught wind of the email from Lionel where Andi was holding the envelope.

Helen emerges, freaking everyone out and making them realize she is Andi’s twin sister. When she presents the napkin to prove that Andi was the true mastermind, Miles burns it, leaving them with zero evidence. The rest of the group is also quiet to speak up for Andi, so Helen tells them they are shitheads. Blanc, having resigned himself to failure, leaves Helen with a drink. As Blanc had earlier said Helen is more quick-thinking when drunk, she downs her drink and begins to break Miles’s various valuable items. The rest of the group then joins Helen in support and starts smashing things, right up until Helen starts a fire. She then presents Miles with the OTHER thing that Blanc left her – a sample of Klear. Helen throws it into the fire, which gets into the vents and creates a massive explosion that destroys the Glass Onion. Blanc and Derol watch from a distance while sharing cigars.

As Miles’s place burns to the ground, Helen decides to pay him back one last favor by opening the case to the Mona Lisa and letting it catch fire. The guests exit, with Miles chastising and mocking Helen, saying that she still has no proof that Andi did anything, but she is content in knowing that she destroyed Miles’s reputation and entire business empire. The rest of the guests then agree to testify against Miles, just as the police start to show up to the island.

Helen then joins Blanc by the water, and she looks to the ocean with a satisfied smirk.

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Tech billionaire Miles Bron of Alpha Industries invites his closest friends - head scientist Lionel Toussaint, Governor Claire Debella, supermodel Birdie Jay, her assistant Peg, Twitch streamer Duke Cody, and his girlfriend Whiskey - to his private island for a murder mystery in his mansion, the Glass Onion. Receiving an unexpected invitation is famous detective Benoit Blanc, along with Miles's former business partner, Cassandra "Andi" Brand, who was screwed out of Alpha by Miles and the rest of the group since he forced them to testify against her.

After Blanc spoils the murder mystery, Duke turns up dead after drinking something that was seemingly meant to poison Miles. Duke's gun goes missing and is used to shoot Andi. Here, the film reveals that "Andi" is really Helen, Andi's twin sister. The real Andi was found dead days earlier from a suspected suicide, but Helen believes that someone in the group murdered Andi because she found an envelope containing a cocktail napkin that she wrote on detailing everything that led to Alpha's success, something that Miles passed off as his own. Blanc worked with Helen for her to infiltrate the party while posing as Andi, gathering motives from the guests. Miles developed an alternative fuel source called Klear, which Andi was against and got her kicked out of the company. Lionel and Claire knew the risks and still signed off on Klear, and Birdie is forced by Miles to take responsibility for a sweatshop that manufactures her clothing line, which Peg fears could cost her her job.

Blanc concludes that Miles was the true killer all along. He killed Andi after learning about the envelope, and Duke was killed after finding out and trying to blackmail Miles for a news position, even trying to get Whiskey to seduce Miles for the job. After Helen reveals herself and finds the envelope, Miles burns it so she has no evidence against him. Helen then chooses to destroy Miles's home, as Blanc had slipped her a sample of Klear, which she uses to blow up the Glass Onion. The rest of the group grows a spine and decides they will testify against Miles, just as police arrive.