In Fail-Safe, a well-known thriller from the 1960s, coauthors Eugene Burdick and Harvey Wheeler fashion an exciting but cautionary tale of what can happen when two countries amass nuclear weapons in a continuous contest to become the mightiest military force on Earth. The novel was written in the midst of just such an astonishing situation, known as the Cold War between the United States and the Soviet Union. The story begins placidly enough, when Russian language expert Peter Buck goes to his office at the White House and begins reading Soviet newspapers. His red phone, a direct line from the President, rings for the first time in his experience, and the plot begins to accelerate. Buck is called to the White House's underground bomb shelter with the President and a few other aides to deal with a possible crisis. At the Air Force's War Room in Omaha, American bombers and fighter planes are in pursuit of an unidentified flying object over Alaska. It turns out to be merely an off-course commercial passenger aircraft, but one group of six bombers flies past the so-called Fail-Safe point, a predetermined point in the sky beyond which they are not allowed to go without direct orders. As War Room officials watch on a large radar screen, the bombers head toward Russia with a full load of nuclear weapons. Unbeknownst to military personnel, an electronic malfunction in the high-technology equipment that monitors fail-safe operations has caused attack orders to be mistakenly sent to the bomber group's commander, Lt. Col. Grady.

Top American military and political leaders are assembled at the Pentagon, where they watch the bombers' progress on a large screen similar to those in Omaha and in the White House bomb shelter. Attempts to contact the bombers by radio fail. Nobody is sure what happened, and much debate ensues over whether it could be mechanical failure or if someone has gone berserk. Both options are widely thought to be unlikely, although General Warren Black, who has been a friend of the President since their college days, holds the minority opinion that mechanical failure is quite possible.

The President orders fighter planes to try to shoot down the bombers, but they cannot catch them before the fighters run out of fuel and crash into the sea. The President then quickly engages in telephone discussions with Premier Khrushchev that are translated by Buck. With the Americans' help, the Russians destroy four of the six bombers, but two nonetheless get through to Moscow, including the one piloted by Lt. Col. Grady. The Russians have scrambled the bombers' radio signals, but now the President contacts Grady and tells him to turn around. Grady's orders at this stage of a fail-safe mission are to ignore voice commands, and he shuts off the radio. The President tells Khrushchev that he realizes the Russians will have to retaliate if Moscow is destroyed. He says to avoid all-out nuclear war, he will order New York City to be destroyed if Moscow is bombed. The President tells General Black to fly over New York. When Col. Grady avoids the last Russian defenses and bombs Moscow instead, General Black follows his orders to drop nuclear bombs on New York, even though his own family is there. He immediately takes poison from his suicide kit. When the President receives word of this act of bravery by Black's copilot, he says that he will recommend the Congressional Medal of Honor for Black.