Nashawn Wade (Kevin Hart) claims that he has loved planes since he was a child, but he has a horrible experience with a typical airline: his dog Dre is classified as a checked baggage instead of a carry-on, he eats a horrible airline meal, his buttocks gets stuck in the toilet while he has diarrhea, caused by his meal, during turbulence, and Dre is fatally sucked through a jet engine after a stewardess accidentally opens the cargo door.
In response to the terrible experience he endured, Nashawn 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, where two non-working TSA Agents, Jamiqua (Mo'Nique) and Shaniece (Loni Love), are goofing off instead of checking belongings. 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 parody of the Destiny's Child song "Survivor".
After taking off from Los Angeles International Airport, Nashawn must deal with a multitude of problems, starting with his acrophobic captain, Captain Mack (Snoop Dogg). At a cruising altitude of Flight Level 330, it is revealed that he has never left the ground because he learned to fly on computer simulators in prison. Meanwhile, his cousin Muggsey (Method Man) sets up a miniature casino and strip joint in one of the areas of the plane (as seen in the workprint and unrated versions of the film), and Nashawn's ex-girlfriend, Giselle (K. D. Aubert) is on board and less than happy to see him. Meanwhile, the Hunkee family, the only caucasian passengers on board, must also deal with their own problems;
Elvis Hunkee's (Tom Arnold) daughter Heather is turning 18 and plans to use her newfound freedom by drinking and having sex, his son has transformed from an exact duplicate of him to a stereotypical wigger, and his wife has found a new interest in black men after viewing pictures in a pornographic magazine.
Captain Mack seemingly dies after eating mushrooms that the co-pilot, First Officer Gaemon (Godfrey), uses to soothe his genital crabs. Nashawn attempts to contact Gaemon, who is incapacitated after slipping near a hot tub, forcing Nashawn to attempt to land the plane himself. Nashawn lands the plane safely, using the airplane stewardess Blanca's (Sofía Vergara) flight knowledge which she learned while having sex in the cockpit with the pilot on another plane. The plane lands in the middle of Central Park instead of John F. Kennedy International Airport, and the spinners are stolen from the plane. Nashawn reconciles with Giselle after earlier revealing to her that he only broke up with her so she would not give up her college opportunities for him.