A former fighter pilot, Ted Striker, is traumatized by his wartime experiences and now fears flying. Striker's fears are exacerbated by the fact that he's still in love with his ex-girlfriend Elaine, a stewardess. In a bid to win her back, he boards the flight she is working on. As the plane advances through its route, several passengers, including the flight crew, are struck down by food poisoning after eating fish. With the pilots incapacitated, Elaine contacts the ground for assistance, and Striker is asked to step up and land the plane despite his deep-seated fear.

On the ground, air traffic controller Steve McCroskey and the eccentric Dr. Rumack guide Ted through the process. Ted's anxiety and flashbacks from the war threaten his ability to focus, but the dire situation forces his hand. Elaine serves as his co-pilot, struggling alongside him to save the lives of everyone on board. Ted must overcome his inner demons and rise to the occasion, relying on his instincts and the support of Elaine and the crew on the ground to bring the flight to a safe landing.