It's been seventeen years (the amount of time between the end of the TV series and this movie) since Oscar and Felix saw each other. Oscar, still a compulsive gambler and untidy slob, is now retired and living in Sarasota, Florida; Felix is still in New York. One day, Oscar is called by his son Brucey (Jonathan Silverman) to invite him to his wedding to Felix's daughter Hannah the following Sunday in California.
Oscar and Felix meet at Los Angeles International Airport and within seconds are at odds with one another. They take a rental car to San Malina for the wedding. But the trip develops into an odyssey, starting with Oscar forgetting Felix's suitcase at the car rental station, and including the complete loss of the written directions to San Malina when Oscar's cigar ash burns them. They lose their way and end up on a small road in the desert; the car rolls off a cliff and catches fire. If that were not enough, they get arrested several times by the local police, first for driving a truck carrying illegal Mexican immigrants, and then for being in a car with a dead man.
Exhausted and believing that they'll never get to the wedding, they get arrested yet again for consorting with armed revenge-hungry rednecks. Released and driven to the local airport by the police, who are only too pleased to be rid of them, they make it to the wedding, but not before Felix meets the "one and only" woman on the airplane.
They arrive to find that Brucey is having second thoughts about the wedding, and Felix and Oscar immediately take sides. But all is resolved and the wedding takes place as planned.