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American and Russian Special Forces capture General Ivan Radek (Jürgen Prochnow), the dictator of a rogue terrorist regime in Kazakhstan that possessed stolen Soviet nuclear weapons, threatening to start a new Cold War. Three weeks after the mission, U.S. President James Marshall (Harrison Ford) attends a diplomatic dinner in Moscow which he praises the capture and insists the United States will no longer negotiate with terrorists. Marshall and his entourage, including his wife Grace (Wendy Crewson) and daughter Alice (Liesel Matthews), and several of his Cabinet and advisers, prepare to return to the United States on Air Force One. In addition, a number of members of the press corps have been invited aboard, including Russian terrorists and Radek loyalists disguised as journalists led by Ivan Korshunov (Gary Oldman).
After takeoff, Secret Service agent Gibbs (Xander Berkeley), who has been a mole, enables Korshunov and his men to obtain weapons and storm the plane, killing many of the other agents and military personnel before taking the civilians hostage. Marshall is raced to an escape pod in the cargo hold while pursued by Korshunov's men but they are too late to capture him as the pod is ejected. Instead, Korshunov storms the cockpit and prevents the plane from making an emergency landing at Ramstein Air Force Base in Germany, and secures Grace and Alice separately from the other hostages. Several F-15s escort Air Force One as Korshunov has it piloted towards Radek-loyal airspace.
Unknown to Korshunov, Marshall, a Medal of Honor recipient, has remained hidden in the cargo hold instead of using the pod, and begins to observe the loyalists using his military training. Marshall manages to kill some of Korshunov's men and then uses a satellite phone to make contact with his Vice President Kathryn Bennett (Glenn Close), letting his staff know he is alive. Korshunov, believing that only a rogue Secret Security agent is in the cargo hold, contacts Bennett and demands Radek's release, threatening to kill a hostage every half hour. Marshall and military advisors devise a plan to trick Korshunov to take Air Force One to a lower altitude for a mid-air refueling, giving time for the hostages to parachute safely off the plane. As a KC-10 tanker docks with Air Force One, Marshall helps to kill another loyalist and escorts the hostages to the cargo hold, where most parachute away; Marshall insists on staying to rescue his family. Korshunov discovers the deception and forces Air Force One away, causing the fuel to ignite, destroying the tanker; the shockwave disrupts the escape process, and Korshunov is able to stop Marshall, Chief of Staff Lloyd Shepherd (Paul Guilfoyle), Major Caldwell (William H. Macy), and Gibbs from escaping.
With the President and his family under his control, Korshunov forces Marshall to contact Russian President Petrov and arrange for Radek's release. Bennett is urged by Defense Secretary Walter Dean (Dean Stockwell) to declare the President incapable under the 25th amendment, so as to override Radek's release, but she refuses. While Korushunov and his men celebrate the news of Radek's release, Marshall breaks his bonds, kills Korshunov's last two henchmen, before strangling and throwing Korshunov off the plane when he tries to escape himself. Marshall races back to lift his order, and Radek is subsequently killed when he attempts to escape.
Marshall and Caldwell direct the plane back to friendly airspace, accompanied by the F-15s, only to be quickly tailed by a second batch of Radek loyalists piloting MiG-29s. Marshall is able to evade most of the missile launches, while one F-15 pilot sacrifices himself to intercept a missile; the resulting explosion damages the plane's tail, and they start to lose altitude. A standby USAF Rescue HC-130 is called to help, sending parajumpers on tether lines to help rescue the survivors. Marshall insists that his family and the injured Shepherd be transferred first. When there is time for only one more transfer, Gibbs reveals himself as the mole, killing Caldwell and the parajumper. Marshall and Gibbs fight for control of the transfer line, and Marshall manages to grab and detach it at the last minute. Air Force One crashes into the Caspian Sea, killing Gibbs. The HC-130 airmen reel Marshall in, who is safely reunited with his family. The HC-130 is subsequently renamed "Air Force One" as they fly back to friendly space.
- Harrison Ford as U.S. President James Marshall
- Gary Oldman as Ivan Korshunov, a Russian Radek loyalist
- Glenn Close as Vice President Kathryn Bennett
- Wendy Crewson as First Lady Grace Marshall
- Liesel Matthews as First Daughter Alice Marshall
- Dean Stockwell as Defense Secretary Walter Dean
- Elya Baskin as Andrei Kolchak, Korshunov's best friend and pilot
- Levan Uchaneishvili as Sergei Lenski, Korshunov's henchman
- David Vadim as Igor Nevsky, Korshunov's henchman
- Andrew Divoff as Boris Bazylev, Korshunov's henchman
- Ilia Volok as Vladimir Krasin, Korshunov's henchman
- Paul Guilfoyle as White House Chief of Staff Lloyd Shepherd
- Xander Berkeley as U.S. Secret Service Special Agent in Charge Gibbs, of Presidential Protective Division.
- William H. Macy as Major Norman Caldwell, military aide to the President
- Alan Woolf as Russian President Petrov
- Tom Everett as National Security Advisor Jack Doherty
- Jürgen Prochnow as General Ivan Radek, the dictator of Kazakhstan
- Donna Bullock as Deputy Press Secretary Melanie Mitchell
- Michael Ray Miller as Colonel Axelrod, pilot of Air Force One
- Carl Weintraub as Lieutenant Colonel Ingraham, co-pilot of Air Force One
- Spencer Garrett as White House Aide Thomas Lee
- Bill Smitrovich as General Northwood
- Glenn Morshower as U.S. Secret Service Agent Walters
- David Gianopoulos as U.S. Secret Service Agent Johnson
- Dan Shor as Notre Dame Aide
- Philip Baker Hall as Attorney General Andrew Ward
- Richard Doyle as Colonel Bob Jackson, Air Force 1 Backup Pilot
- Willard Pugh as White House Communications Officer
- Don R. McManus as Lt. Colonel Jack Carlton, F-15 "Halo Flight" Leader
- J.A. Preston as the USAF Major General who was President Marshall's Commanding Officer during the Vietnam War