John Beckwith (Owen Wilson) and Jeremy Grey (Vince Vaughn) are divorce mediators in Washington D.C. The two friends frequently "crash" wedding parties to meet and bed women, working from a set of rules taught to them by a retired crasher, Chazz Reinhold (Will Ferrell). The duo always has cover stories for inquisitive guests and inevitably become the hit of every reception by using their charm and lies to avoid being caught. Their goals are to enjoy the free food and drinks and ultimately to charm their way into bed with women from the wedding for a one-night stand. After a sequence of successful crashes, Jeremy takes John to a wedding for the 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 while the reception is taking place. Gloria is possessive and quickly becomes obsessed with Jeremy. She claims to have been a virgin until the encounter, which shocks Jeremy, and he tries to get John to bail on the reception with him.
Meanwhile, John is attempting to court Claire, the maid of honor, but he is interrupted by her hotheaded boyfriend, Sack Lodge (Bradley Cooper), who later turns out to want to date Claire only because of William's political power and is shown to openly mock and cheat on her behind her back. Later, John convinces Jeremy to accept the family's invitation to an extended weekend party at their family compound. Once there, Jeremy, John, and other members of the family play a game of touch football, which ends with Jeremy being badly hurt by an over-aggressive Sack. Gloria tends to him, while trying to engage him in sexual intercourse at the same time. At dinner later that evening, Gloria gives Jeremy a hand job under the dinner table, while John spikes Sack's wine with eye-drops. Sack becomes sick, which lets John further connect with Claire, and they agree to go for a walk together following dinner. John goes to his room to change his shoes, but William's wife, Kathleen (Jane Seymour), makes John fondle her surgically enhanced breasts, then rebuffs his actions, much to John's confusion. Later that night, Gloria ties up Jeremy and proceeds to have sex with him, saying she is being "adventurous" and is fulfilling fantasies. That same night, Gloria's gay brother, Todd (Keir O'Donnell), paints a provocative portrait of Jeremy and tries to seduce him, but is interrupted by his father. The next morning, Jeremy asks John if they can go home, but John convinces him to stay, which helps Jeremy realize that John is falling for Claire.
That afternoon, the family (minus Sack) go sailing, where John and Claire continue to bond. Following the sailing trip, the family (with Sack now joining them) go on a hunting trip, where Sack intentionally shoots in the direction of Jeremy and John, shooting Jeremy in the buttocks. After the hunting trip, John and Claire go on a bike ride through the country, and they end up at a secluded beach. Claire finally admits she isn't sure how she feels about Sack, and ends up kissing John passionately. Meanwhile, Gloria is tending to Jeremy's wounds, and reveals to Jeremy that she was not a virgin when they met, and that she only said that because that's what she thought he would like to hear. Jeremy realizes that he may be in love with Gloria. Later that day while eating lunch, Sack announces (untruthfully) that he and Claire are engaged, leaving Claire at a loss for words. Outside, John is about to convince Claire to be with him, when they are interrupted by Jeremy being chased out of the house. Sack emerges and forces John and Jeremy to tell the truth about who they really are, as he had them privately investigated. John reluctantly reveals their true identities, and William kicks them out. While leaving, Todd wants his portrait back, but Jeremy tells him that he's keeping it as a gift; this gives Todd some relief knowing that someone took him seriously as an artist. Jeremy and Gloria briefly confess their love to each other.
John and Jeremy return to their normal lives. During that time, Jeremy is trying to keep his relationship with Gloria a secret when John comes in to talk to him. He has formulated a new way to try and reconcile with Claire by trying to be a waiter at her engagement party. Jeremy tries to convince him that his attempts to reconcile with her were unsuccessful and he needs to let it go by coming to terms with the fact that Claire doesn't want anything to do with him. While pretending to be a waiter, he is caught and brutally beaten by Sack while his friends hold John. Once he recovers, he goes to search for Jeremy (who was supposed to have helped him), but instead finds him still at his house and having sex with Gloria. When John learns the truth, he's very upset by it and it causes a rift between him and Jeremy. John crashes several more weddings alone, but behaves erratically due to his state of depression, and soon becomes nihilistic and suicidal. Meanwhile, Jeremy continues his relationship with Gloria, culminating in an accepted marriage proposal, and Claire begins to doubt her relationship with Sack. Jeremy attempts to reconcile with John, asking him to be his best man, but John refuses. John then goes to meet their mentor, Chazz Reinhold (an uncredited Will Ferrell), to reaffirm Jeremy's apparent stupidity in getting engaged. During the visit, Chazz talks him into crashing a funeral instead of going to Jeremy's wedding, as Chazz believes that grief is the best aphrodisiac. While there, John takes notice of a woman who is truly grieving for her husband because she loved him. He reconsiders his stance on love and marriage and rushes to Jeremy's wedding.
John joins the wedding mid-ceremony to Jeremy's delight, but soon disrupts it by attempting to speak to Claire. Claire, in tears, leaves the altar, but John quickly professes his love to her and his feelings of regret of his past behavior towards women. Sack interrupts, asking Claire to return to the altar so the wedding can be finished. Claire finally tells Sack that she can't marry him. He turns to William for help, but instead William states his full support of his daughter's decision to reject Sack, after he admits he put up with him because he thought Claire was happy. Clearly angry, Sack begins aggressively demanding Claire to return to the altar. John states that everyone is getting a good preview of what it would be like to be married to Sack (whom he refers to as Ike Turner, referencing his abuse of his ex-wife Tina). Sack loses control of himself completely and rushes at John, but Jeremy intervenes and knocks him out.
The film ends with Jeremy getting married to Gloria, John uniting with Claire, and the two couples driving away talking about crashing another wedding together.