Ex-fighter pilot Ted Striker is a traumatized war veteran turned taxi driver. Because of his pathological fear of flying and “drinking problem” (being unable to take a drink without splashing it on his face), he has been unable to hold a responsible job. His wartime girlfriend, Elaine Dickinson, now a flight attendant, leaves him before boarding her assigned flight from Los Angeles to Chicago. Ted abandons his taxi and buys a ticket on the same flight to try to win her back. However, she still continues to reject him during the flight.
After the in-flight meal is served, several of the passengers and the flight crew fall ill, including Captain Oveur. Passenger Dr. Rumack discovers one of the offered courses caused food poisoning. With the flight crew incapacitated, Elaine contacts the Chicago control tower for help, and is instructed by tower supervisor Steve McCroskey to activate the plane’s autopilot, a large inflatable pilot doll named “Otto”, which will get them to Chicago, but will not be able to land the plane. Elaine and Dr. Rumack convince Ted to take the controls. When Steve learns that Ted is piloting, he contacts Ted’s former commanding officer, Rex Kramer, now serving as a commercial pilot, so that he can help talk Ted through landing the plane. Ted becomes troubled when Rex starts giving instructions, and briefly stresses out from flashbacks to the war. Both Elaine and Dr. Rumack bolster Ted’s confidence and he takes the controls under Rex’s guidance.
As the plane nears Chicago, the weather becomes harsh, making landing difficult. With Elaine’s help as co-pilot and Rex’s guidance, Ted is able to land the plane safely with the passengers suffering only minor injuries, despite the landing gear being sheared off. Rescue vehicles arrive to help unload the plane. Impressed by Ted’s display of courage, Elaine embraces and kisses him, rekindling their relationship. The two watch as “Otto” takes control of the plane, inflates a female companion, and takes off.