John Beckwith (Owen Wilson) and Jeremy Grey (Vince Vaughn) are divorce mediators in Washington D.C. who "crash" wedding parties to meet and bed women. At the end of a season of successful crashes, Jeremy takes John to a wedding for a daughter of the U.S. Secretary of the Treasury, William Cleary (Christopher Walken). Once inside, the pair set their sights on Cleary's other daughters, Gloria (Isla Fisher) and Claire (Rachel McAdams). Jeremy ends up having sex with Gloria on a nearby beach during the reception. Gloria is possessive and quickly becomes obsessed with Jeremy, and Jeremy urges John to escape the reception with him.
Meanwhile, John attempts to court Claire, the maid of honor, but is interrupted by her hotheaded boyfriend, Sack Lodge (Bradley Cooper), who is unfaithful and disrespectful behind her back. When Gloria invites Jeremy and John to an extended weekend party at their family compound, Jeremy tries to refuse due to him being extremely uncomfortable with Gloria. John overrules Jeremy to accept as it would be great to get to know the family. Jeremy reluctantly accepts, although he is suspicious that John only wanted to go just to get closer to Claire.
John and Jeremy become acquainted with the Clearys at their home: the Secretary's wife (Jane Seymour) sexually harasses John; Gloria's brother Todd (Keir O'Donnell) tries to seduce Jeremy during the night; Gloria continues to lavish unwanted sexual attention on Jeremy; and Sack repeatedly injures Jeremy during a game of touch football. During dinner, as a means to get even with Sack for injuring Jeremy along with more time to connect with Claire, John spikes Sack's wine with eye-drops to make him sick and he spends the rest of his night throwing up in the toilet.
John and Claire continue to bond the next day on a sailing trip. The suspicious Sack calls his friend, Trapster, to privately investigate John and Jeremy. He then takes Jeremy hunting, where he is shot in the buttocks. While he recovers, John and Claire go on a bike ride to a secluded beach. Claire finally admits she is unsure how she feels about Sack and ends up kissing John passionately. Meanwhile, Gloria tends to Jeremy's wounds and reveals to him that she is not as innocent or inexperienced as she initially let on. Jeremy realizes that he himself has been played and that he may be in love with Gloria. When Sack falsely claims that he and Claire are engaged, John isn't fooled by this attempt knowing how unhappy she is with him.
Ready to confess everything to Claire about his feelings for her and convince her not to marry Sack, John is interrupted by Jeremy being chased out of the house. Sack reveals John and Jeremy's identities to the family. Betrayed, Claire turns away from John and the Secretary tells them to leave. Gloria tells Jeremy she loves him regardless of his fraudulence.
Over the following months, Jeremy manages to keep his relationship with Gloria a secret. Meanwhile, John attempts to reach Claire but she refuses to see him. He comes up with a plan to see her by disguising himself as a waiter at her and Sack's engagement party. Concerned about John's behavior, Jeremy tries to talk some sense into him by reminding him that his last attempts to speak to her has failed and that he needs to accept the fact that it's over. He also warns John against attempting to crash Claire and Sack's engagement party because of the security of Secretary Cleary’s Secret Service protection. Jeremy mentions that their only chance of avoiding jail time is to keep a low profile and stay away. John ignores the warning and goes forward with his crash plans. Sack catches him and beats him up. John visits Jeremy at his house to confront him for his absence and catches him having sex with Gloria. Betrayed, John walks out of the house and Jeremy follows trying to explain himself, while Gloria leaves to go to the engagement party. Outside, John demanded why he didn't appear to stop Sack and learns that Jeremy had continued his secret relationship with Gloria. John spirals into depression, crashing weddings alone and becoming nihilistic and suicidal. While planning her wedding, Claire's doubts about Sack begin to grow. Jeremy proposes to Gloria and tries to ask John to be his best man, but a depressed John refuses.