Gaylord "Greg" Focker is a nurse living in Chicago. He intends to propose to his girlfriend, Pam Byrnes, but his plan is disrupted when they are invited to the wedding of Pam's sister, Debbie, at their parents' house on Long Island. Greg decides to impress Pam's parents first, and propose to her in front of her family, but this plan is put on hold when the airline company loses his luggage which contains the engagement ring.
At the Byrnes's house, Greg meets Pam's father, Jack, mother, Dina, and their beloved cat, Jinx. Despite maintaining a friendly demeanor towards him, Jack is immediately suspicious of Greg and openly criticizes him for his choice of career as a male nurse and anything else he sees as a difference between Greg and the Byrnes family. Greg attempts to impress Jack, but his efforts fail. He becomes even more uncomfortable after he receives an impromptu lie detector test from Jack and later learns from Pam that Jack is a retired CIA operative.
Meeting the rest of Pam's family and friends, Greg still feels like an outsider. Despite efforts to impress her family, his inadvertent actions make him an easy target for ridicule. Greg unintentionally gives Debbie a broken nose and a black eye during a pool volleyball game, uses a malfunctioning toilet which floods the Byrnes' backyard with sewage, and sets the wedding altar on fire. Several misunderstandings also cause Jack to believe Greg is a marijuana user after Pam's weed-using brother, Denny, unintentionally frames him. Later, Greg loses Jinx and replaces him with a stray whose tail he spray paints to make him look like Jinx which happens to also make a mess of the house (though the real Jinx is later found). By now, the entire Byrnes family, including Pam, agrees that it is best for Greg to leave Long Island until the wedding concludes. Desperate to save himself, Greg reveals he has seen Jack engaging in some secret activity with some shady characters, and that Jack is planning a secret mission after the wedding. Jack angrily reveals that the secret mission was a surprise honeymoon for Debbie and her fiancé Bob, and Greg realizes he has only dug himself deeper into a hole.
Unwillingly, Greg goes to the airport where he is detained by airport security for insisting that his luggage stays with him rather than be checked. Back at the Byrnes's house, Jack learns from a disappointed Pam that Greg's real name is Gaylord, and is presented with proof that Greg passed the Medical College Admission Test. Despite this, Jack still states his belief that Greg is an unsuitable husband for Pam because of the mistakes and lies he made, but is told off by Dina over his consistent picking apart of any man Pam brings home (and that he didn't even like Pam's previous fiancé, Kevin, until after they broke up). After hearing Pam make a heartfelt phone call to Greg to apologize for not sticking up for him earlier, Jack realizes that Pam truly loves Greg. He rushes to the airport, convinces airport security to release Greg, and brings him back to the Byrnes's house.
As Greg is proposing to Pam, Jack and Dina listen in on their conversation from another room, agreeing that they should now meet Greg's parents (though both are visibly worried about this). After Debbie's wedding, Jack views footage of Greg recorded by hidden cameras that he had placed strategically around the house in which Greg calls Jack a "psycho" and mocks him and exposes Denny as the true marijuana user.
Robert De Niro as Jack Byrnes, a retired CIA agent and a Vietnam War veteran who is overprotective of his family and takes an instant dislike towards Greg
Ben Stiller as Greg Focker, a male nurse and Pam's boyfriend, who seeks to impress her parents
Teri Polo as Pam Byrnes, a 2nd grade teacher, who is Greg's girlfriend and Jack and Dina's older daughter
Blythe Danner as Dina Byrnes, Jack's wife and Pam's mother
Nicole DeHuff as Debbie Byrnes, the younger sister of Pam, Jack and Dina's younger daughter and Bob's fiancée
Jon Abrahams as Denny Byrnes, brother of Pam and Debbie, and Jack and Dina's youngest child
Owen Wilson as Kevin Rawley, the wealthy stock investor/carpenter ex-fiancé of Pam
James Rebhorn as Larry Banks, Bob's father and a close friend of Jack, who is a plastic surgeon
Thomas McCarthy as Bob Banks, Larry and Linda's son, a doctor and Debbie's fiancé
Phyllis George as Linda Banks, Larry's wife and Bob's mother
the film inspired two sequels, namely Meet the Fockers and Little Fockers