During the COVID-19 pandemic in May 2020, Miles Bron, the billionaire owner of Alpha Technology, hosts a murder mystery game at Glass Onion, his island mansion in Greece. He invites five friends: Alpha’s chief scientist Lionel Toussaint, Connecticut Governor Claire Debella, fashion designer and models Birdie Jay, men’s rights activist Duke Cody and Alpha’s ousted founder Cassandra “Andi” Brand. The five friends got a wooden puzzle box to figure out to find the invitation inside. The five travel to Miles Island, along with Birdie’s assistant, Peg, and Duke’s girlfriend, Whiskey. They are joined by the famous detective Benoit Blanc; even though Miles says he didn’t invite Blanc, he lets Blanc stay, thinking another guest sent him an invitation as a joke.
Before dinner, Miles shows off his prized glass figurines, as well as the Mona Lisa, which he borrowed from the Louvre. Miles also reveals that the building is sponsored by “Klear”, an alternative hydrogen-based fuel that Alpha will soon launch, despite Lionel and Claire’s concerns that it is untested and dangerous. Blanc immediately solves the mystery of Miles’ murder and secretly warns Miles that his guests have plans to kill him. After arguing with others, Andi left. Duke dies after drinking from Miles’ glass, and the terrified group suspects Andi of trying to kill Miles. The police were called but would only come in the morning. After the team discovers Duke’s gun is missing, the power is cut and everyone goes their separate ways. In the dark, White finds Andi but is run over by an unseen attacker. White gathers the team and announces that he has solved Andi’s murder.
A further extension reveals that Andi died a week earlier, apparently by suicide; Blanc was hired by her twin sister Helen to investigate. At Alfa, Andi stopped the development of Klear due to dangerous reasons, so Miles removed him as CEO; Friends who assisted in his trial testified that Miles had single-handedly written the Alfa plan on a canvas years ago. The towel is Andi’s work; Shortly before his death, he sent a photo to the group showing the original towel still in his hand. Helen suspects that one of the groups killed Andi and stole the towel to protect Miles. With Andi’s death not yet public knowledge, Blanc persuaded Helen to impersonate Andi at Miles’ party and help investigate.
Helen helps Blanc uncover Miles’ friends’ motives for protecting Miles from Andi: Lionel and Claire have staked their reputations on Klear, Miles financially saves Birdie from the fallout of sweatshop employment, and Duke hopes that Miles will help him. will give a show on Alpha Nouvelles. Helen finds out that every one of Miles’ friends went to Andi’s house the day she died. He checks the guest room and doesn’t find the towel. When Helen was shot, Andi’s notebook in her jacket pocket stopped the bullet. Blanc fakes her death to search Miles’ office.
Blanc finds out that Miles killed the two. He kills Andi when he realizes she has the towel, but Duke sees her leaving the house in his car. During the party, Duke sees the news about Andi’s death and, realizing that Miles was responsible, tries to destroy it. This causes Miles to poison her with pineapple juice, which Duke pains her, and takes Duke’s gun, which he uses to shoot Helen. Helen finds Andi’s bag in Miles’ office and reveals her identity to the team. However, Miles burns the towel, destroying the evidence, and his friends refuse to testify against him. Blanc tells Helen that she did everything she can and gets out. In a fit of rage, Helen destroys Miles’ cup sculpture; Miles’ friends watch him and eventually join him. Helen lights a fire and throws a shard of Klear Blanc that falls into it, causing a dangerous explosion, and destroying the building and the Mona Lisa. Realizing that destroying the painting will reveal that Klear is dangerous and harm Miles, the group decides to testify against him. On the beach, Helen and Blanc watch the police boat arrive.