Ex-fighter pilot Ted Striker is a traumatized war veteran turned taxi driver. Because of his pathological fear of flying and subsequent "drinking problem"—he splashes beverages anywhere but into his mouth—Ted has been unable to hold a responsible job. His wartime girlfriend, Elaine Dickinson, now a flight attendant, breaks off her relationship with him before boarding her rostered flight from Los Angeles to Chicago. Ted abandons his taxi and buys a ticket on the same flight to try to win her back. Once on board, however, Elaine continues to reject him, causing Ted to accidentally drive several other passengers to suicide as he sadly reminisces.
After the in-flight meal is served, the entire flight crew and several passengers fall ill. Passenger Dr. Rumack discovers that the fish served during meal service has 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 dummy pilot dubbed "Otto", which will get them to Chicago but not be able to land the plane. Elaine and Rumack convince Ted to take the controls. When Steve learns Ted is piloting, he contacts Ted's former commanding officer, Rex Kramer—now serving as a commercial pilot—to help talk Ted through the landing procedure. Ted becomes uneasy when Kramer starts giving orders and he briefly breaks down amid more wartime flashbacks. Elaine and Rumack both bolster Ted's confidence and he manages to once again take the controls.
As the plane nears Chicago, the weather worsens, complicating the landing. With Elaine's help as co-pilot and Rex's guidance from the tower, Ted is able to land the plane safely, despite the landing gear shearing off, and the passengers suffer only minor injuries. 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.
