30 years later... Oscar has settled in Sarasota, Florida, where he reports on a weak minor league baseball team and plays cards with other senior citizens. His son notifies him from California that he's getting married in a few days, to the daughter of Felix Ungar.
Oscar and Felix happily reunite at the Los Angeles airport, 17 years after living together in New York City, but having not seen each other since then. They rent a car and drive off together, promptly teasing each other about their annoying differences: Felix was always fastidious and clean, Oscar was always unkempt and casual.
Oscar soon gets irritated with Felix for needing to stop to pee, and later needing to stop for food, and to take pills. Felix laments that his third wife left him a few years earlier.
Within a couple hours of driving, the two lose the directions to the wedding, realizing that Felix's suitcase was left back at the car rental agency. Making matters worse, the empty rental car rolls down a hillside and explodes.
Felix and Oscar set off on foot along the desert highway, and no other cars come by for hours. They finally get picked up by a Mexican farmer, who asks them to drive his truck to a nearby gas station. They are soon stopped and arrested by a phalanx of police who find many illegal immigrants in the back of the truck.
The local sheriff deduces that the two are not criminals and lets them go. Felix calls relatives at the wedding site and learns that they are five hours off course, so he and Oscar decide to spend the night in their current town.
Felix and Oscar go off to a local bar, where Oscar charms a couple ladies somewhat younger than they are, named Thelma and Holly, and Felix goes along. The two couples dance, until the ladies suddenly need to leave.
The next morning, they get a ride with an older man who is heading to the town where the wedding is being held. Alas, he soon dies after driving the car very slowly for a few miles. Police show up and take Felix and Oscar back to town, where the same sheriff from before again deduces they have committed no crimes and lets them go.
Felix and Oscar get a bus out of town, and Felix says he feels happy and youthful. Along a stop, Thelma and Holly get on the bus, but soon after, the ladies' husbands hijack the bus and take all of them hostage on a wild car ride. Soon the police stop them and take them back to the same town where the same sheriff from before becomes so frustrated that he offers to transport Oscar and Felix to the wedding by a regional airline.
While getting on the plane, Felix meets a friend of Oscar's named Felice, whom he is sure is his soulmate. Oscar convinces Felix to chat up Felice, and the three continue on to the wedding.
When they arrive, they immediately learn that Oscar's son-- the groom-- has gotten cold feet and is hiding on the roof. Oscar tries to talk him out of getting married, in reverse psychology that convinces his son to go through with the wedding.
After the service, Felix dances with Felice. Oscar gives his son extremely valuable baseball cards as a gift. That night, Felix tells Oscar that he plans to spend some time in San Francisco with Felice.
Felix and Oscar depart at the airport with restrained emotion.
Back in Sarasota, Felix shows up at Oscar's house to tell him that things did not work out with Felice. Oscar is hesitant, but agrees that Felix can stay with him for a while. As Felix begins cleaning the place, Oscar goes back to playing poker with his old friends.