Kazakhstan warlord Uli Radek is captured by joint American-Russian forces and placed in a Russian maximum security prison. At a dinner is Moscow, US President James Marshall apologizes for not acting sooner, as he believes that Radek could have been stopped sooner. He vows to never negotiate with terrorists.
Following the dinner, Marshall boards Air Force One with his family to return home to the United States. A news group also boards the flight. However, they are in fact six Radek loyalists, led by Ivan Korushnov, who murdered the real news group and disguised themselves. Also in on the plot is Secret Service mole Agent Gibson.
Once the plane takes flight, Gibson murders the people guarding the plane's armoury, allowing Korushnov and his men to storm it and then take over the plane. The cockpit is breached and the pilots are murdered while President Marshall is smuggled to an escape pod. The terrorists then take his wife and daughter hostage.
Korushnov then contacts the White House Situation Room, where he speaks to Vice President Kathryn Bennet. The military locates the escape pod, only to find it empty. They realise that the President is still on board. The terrorists do not realise, nor do they know that he is a former soldier and retired aviator. He contacts Bennet and tells her not to negotiate with terrorists.
Marshall decides to drain the fuel from the plane, which will force the terrorists to allow for a mid-air refueling, during which the hostages can parachute away. However, Korushnov destroys the refueling plane and then captures Marshall. Meanwhile, Bennet contacts the Russian President Petrov and arrange for Radek to be released.
Marshall frees himself as Korushnov and his men celebrate, before Korushnov realises and takes Marshall's wife as a hostage. Marshall pursues them to the cargo hold, which Korushnov opens, threatening to throw Marshall's wife out, only for her engage in a scuffle with Korushnov. Marshall then jumps on Korushnov and wraps a rope around his neck before pulling open his parachute. Korushnov is caught in the slipstream and pulled out, and is ultimately strangled by the cord.
Marshall sends out word that Korushnov has been defeated and Radek's escape is halted. As he tries to jump into the waiting helicopter, he is gunned down. Kazakh fighter jets arrive and attempt to shoot down Air Force One, while American fighters intercept them. They ultimately take down the enemy fleet but the battle damages the plane. It is decided that zip-line will be used to rescue the people on board Air Force One.
Marshall orders that his family and friends be rescued first. Ultimately, only Marshall, Gibson and Marshall's loyal advisor Major Cauldwell remain on the plane. Gibson, his sanity having been slipping the entire time, tries to shoot Marshall but Cauldwell steps into the bullet's path and is killed. Marshall escapes on the zip-line as it breaks away from the plane. The plane finally crashes into the ocean, killing Gibson. Marshall is reunited with his family and returns to friendly air space.
Denzel Washington - US President James Marshall
Sigourney Weaver - US Vice President Kathryn Bennet
Thandie Newton - First Lady Grace Marshall
Zendaya Coleman - First Daughter Alice Marshall
Alfred Molina - Uli Radek
Mads Mikkelsen - Ivan Korushnov