In the near future, the Moon has been colonized and supports a station on its surface. A lunar shuttle known as Mayflower One is being rushed to launch from Houston. The head of the ground crew, The Sarge (Chuck Connors), does not like what is occurring, but he defers to the airline's management.
When the Twin Towers went down in 2001, Charlie Fineman (Sandler) lost everything important in his life. Five years have passed since Charlie's wife and daughters died, and now the once-successful and sociable man has become a withdrawn shadow of his former self.
When an Amacore oil rig in the Gobi Desert of Mongolia proves unproductive, Captain Frank Towns (Dennis Quaid) and co-pilot A.J. (Tyrese Gibson) are sent to shut down the operation and transport the crew (Ian, Kelly, Rodney, Davis, Liddle, Jeremy, Sammi, Rady, Kyle, Newman, and Dr. Gerber) out of the desert. However, en route to Beijing, a major dust storm disables one engine, forcing them to crash land their C-119 Flying Boxcar in an uncharted area of the Gobi Desert. Kyle falls to his death and the crash kills Dr. Gerber and Newman. Their cargo consists of used parts and tools from the rig, the rig's crew, and Elliot (Giovanni Ribisi), a hitchhiker. When the dust storm ends, it becomes apparent that they are 200 miles off course with only a month's supply of water. Jeremy (Kirk Jones), thinks about walking to get help, but Rady (Kevork Malikyan) explains that July is the hottest in the Gobi, and that he won't make it.
University of Central Arkansas student Chloe Steele has flown in from college to surprise her father, pilot Rayford Steele, for his birthday party. Her mother Irene Steele quickly calls to inform her, however, that her father cannot make it. While at the airport waiting for him, Chloe meets up with investigative reporter Cameron "Buck" Williams.
Donna Jensen is a girl from a small town in Nevada who wishes to see the world in order to get away from her unhappy life of living in a trailer with her alcoholic mother, a former Las Vegas showgirl, and her abusive, alcoholic stepfather, where she feels miserable and lonely. After graduating from high school, Donna tries to make ends meet by working as a clerk in a Big Lots.
The film opens up on Operation Eagle Claw, the American operation to rescue American hostages being held at the U.S. embassy to Tehran. The operation is being aborted after a fatal helicopter crash, with the U.S. Delta Force evacuating to their C-130 transports. Among them is Captain Scott McCoy, who, against orders, rescues his wounded comrade Pete Peterson from the burning helicopter before the team finally evacuates. McCoy expresses his disgust for the politicians and military hierarchy that forced the mission to launch despite the risks, and announces he is resigning his commission.
L'histoire vraie de l'hôtesse de l'air de 22 ans, Neerja Bhanot (Sonam Kapoor), tuée à Karachi en 1986, lors du détournement du vol 73 Pan Am, dans lequel elle était chef de cabine, alors qu'elle sauvait la vie de 360 passagers.
Nashawn Wade (Kevin Hart) has a horrible experience with a typical airline: his dog is classified as checked baggage instead of a carry-on, he eats a horrible airline meal, his buttocks gets stuck in the toilet during turbulence, and Nashawn's dog is sucked through a jet engine (after accidentally opening the cargo door). In response, he sues the airline and is awarded $100,000,000 by the jury. He decides to use the money to start his own airline, called N.W.A. (Nashawn Wade Airlines), whose acronym and logo are a pop culture reference to rap group N.W.A. The airline, specifically caters to African Americans and hip hop culture. The terminal at the airport is called the Malcolm X terminal, the plane is a heavily modified Boeing 747SP, customized with low-rider hydraulics, spinners, blended winglets to compensate for the drag from the decorations, and a dance club. The safety video is also a spoof of the Destiny's Child song "Survivor".
Kevin Harrison (Robert Wagner), a corrupt arms dealer, attempts to destroy an American-owned Concorde on its maiden flight after one of the passengers, reporter Maggie Whelan (Susan Blakely), learns of his weapons sales to communist countries during the Cold War.
In May 1969, Lou Jean Poplin (Goldie Hawn) visits her husband Clovis Michael Poplin (William Atherton) to tell him that their son will soon be placed in the care of foster parents. Even though he is four months away from release from the Beauford H. Jester Prison Farm in Texas, she forces him to escape to assist her in retrieving her child. They hitch a ride from the prison with an elderly couple, but when Texas Department of Public Safety Patrolman Maxwell Slide (Michael Sacks) stops the car, they take the car and run.
The film opens as ground technician León (Antonio Banderas) removes the chocks from the wheels of an Airbus A340 for Peninsula Flight 2549. He waves to his wife Jessi (Penélope Cruz ), who is towing a luggage cart across the tarmac. The distraction causes her to crash into another ground technician who was checking Twitter. León checks on his wife to make sure she is okay, and she reveals that she is pregnant.
After Ryan Weaver is arrested for a murder that he says he did not commit, he must be transported to Los Angeles to face trial. He and another prisoner are escorted by four air marshals on a Boeing 747 on a commercial flight. Even though it is Christmas Eve, the 747 is nearly empty, with only 11 people on board. The entire cabin is highly decorated with Christmas trees and other decorations.
A jaded pilot named Noah Dugan (Gould) is unemployed and owes a large amount of money due to his gambling. He goes to an old friend, Stoney (Vincent Gardenia), who owns an airfield. He is offered a job flying a cargo of animals to a remote South Pacific island aboard a B-29 bomber, a large plane well past its prime (having born the brunt of U.S. combat against Japan decades earlier during World War II). Bernadette Lafleur (Bujold) is the prim missionary who accompanies him. Bernadette has raised the animals at an orphanage and is close to two of the orphans, Bobby and Julie (Schroder and Tammy Lauren).