The bow (front) of the aircraft is referred to as the "White House" of the plane. The president's executive suite includes sleeping quarters with two couches that can be converted into beds, lavatory and full-ranged shower, vanity, double sink, and a private office, or the president’s "Oval Office aboard Air Force One". If necessary, the president can address the nation from the office. This capability was added after the September 11 attacks, during which the plane had to land at Barksdale Air Force Base in order for President Bush to address the nation. These offices, including the president's suite, are mostly located on the starboard (right), and a long corridor runs along the port (left) side. There is an area along the corridor for two Secret Service agents. The plane also contains a conference room, originally designed as situation room but now used for meeting with staff while traveling. This room includes a 50-inch plasma screen television which can be used for teleconferencing. The planes have fully equipped office areas with telecommunication systems (including 87 telephones and 19 televisions).

The VIP compartment can be converted to a medical facility for minor medical emergencies. The medical annex includes a fold-out operating table, emergency medical supplies, and a well-stocked pharmacy. Every flight is staffed by a doctor and nurse.

President George W. Bush had a treadmill added to Air Force One during his term in office. Chief Flight Attendant Reggie Dixon said, "Air Force One will leave Andrews Air Force Base self-contained," meaning that no matter how long the trip, the plane leaves with all the food it will need. Meals are prepared in two galleys, which together are equipped to feed up to 100 people at a time. The President gets his own menu. Near the center of the plane, outside of what is referred to as "the White House", is an area where guests sit.

There are separate quarters for guests, senior staff, Secret Service and security personnel, and the news media located in the aft (back) of the second floor. Protocol states that wherever one's assigned seat is, they may wander aft of that seat, but not forward. Communications equipment and the cockpit are on the third floor. There are also secure and non-secure voice, fax and data communications facilities.

While the plane's luggage capacity is adequate to carry the belongings of the passengers, the logistics train of the President means that the plane must fly preceded by an aerial convoy of several cargo transports, which carry the helicopters, motorcade vehicles, and other equipment required by the presidential entourage.

The VC-25A is capable of flying 7,800 miles (12,600 km)—roughly one-third the distance around the world—without refueling. It can be refuelled during flight from a tanker aircraft. The VC-25A can accommodate more than 70 passengers. Each VC-25A cost approximately US$325 million. When a VC-25 taxis to an airport's ramp for events, it comes to a stop with the port side of the aircraft facing gathered onlookers.

Operational history
The VC-25s replaced the VC-137C (a military version of the Boeing 707) as the mainstays of the Air Force One fleet. On some occasions, the VC-25s are used to transport the Vice President of the United States, for which service they adopt the callsign Air Force Two. These aircraft are maintained and operated as military operations by the Presidential Airlift Group, part of Air Mobility Command's 89th Airlift Wing, based at Andrews Air Force Base in Camp Springs, Maryland.

The airplanes can also be operated as a military command center in the event of an incident such as a nuclear attack. Operational modifications include aerial refueling capability and anti-aircraft missile countermeasures. The electronics on board are connected with approximately 238 miles (383 km) of wiring, twice that of a regular 747. All wiring is covered with heavy shielding for protection from an electromagnetic pulse in the event of a nuclear attack. The planes also have electronic countermeasures (ECMs) to jam enemy radar, flares to avoid heat-seeking missiles, and chaff to avoid radar-guided missiles. All small arms and ammunition stores not under the physical possession of the Secret Service on board the VC-25s are stowed and secured in separate locked compartments each with a different locking mechanism by the Secret Service for added security. Many of the VC-25's other capabilities are classified for security reasons.

At the Presidential inauguration in which there is a change in office, the outgoing President is provided a flight aboard one of the VC-25A planes to their home destination. The plane is not known as Air Force One for this flight because it is not carrying the President in office. For both Presidents Bill Clinton and George W. Bush, the flight was known as Special Air Mission 28000, with 28000 representing the plane's tail number.

The VC-25A has also been used to transport deceased former presidents. The guest area aft of the "the White House" has chairs and tables that can be removed and the casket laid in their place. The remains of both Ronald Reagan and Gerald Ford were transported by SAM 28000 and 29000 respectively to Washington for their state funerals, and then on to their final resting places. Colonel Mark Tillman, pilot for President George W. Bush, said, "We’ll take care of the president from basically when he’s in office to when he lays in state." For the funeral of President Ronald Reagan in 2004, Tillman said that the crew converted the front of the aircraft to look the way it would have appeared when Reagan was president; President and Nancy Reagan’s Air Force One jackets were placed on the chairs to “make them at home”. A specially designed hydraulic lifter (similar to the type used by airline catering) with the presidential seal affixed to the sides lifts the casket up to the door to enter the VC-25A. The tradition of placing the caskets inside the passenger cabin dates back to the assassination of John F. Kennedy, when the crew refused to allow the president's body to be placed in the cargo hold. This was also evident during the state funeral of Lyndon B. Johnson.

Future
These aircraft are expected to be replaced as they have become less cost-effective to operate. The USAF Air Mobility Command is looking into possible replacements including the Boeing 747-8 and the Airbus A380. On January 7, 2009, the USAF Materiel Command issued a new Request For Proposals (RFP) for a replacement aircraft to enter service by 2017 with an additional two aircraft to follow in 2019 and 2021. As of January 2009, Boeing is the only interested vendor in supplying the replacement aircraft, and is reported to be exploring a 787 option as well. On January 28, 2009, EADS North America confirmed the company will not respond to a US Air Force Request For Information (RFI). EADS decided it was not in the best interest of the company to pursue.