In 1961, the United States had deployed 15 PGM-19 Jupiter intermediate-range nuclear missiles to the Çiğli air base near İzmir in Turkey — some 16 minutes' flight time from Moscow. To the Soviets this was an intolerable asymmetry; in the summer of 1962 Khrushchev quietly decided to place similar missiles in Cuba — 150 km from Florida. Operation Anadyr began in summer 1962; between September and October some 42 R-12 and R-14 nuclear missiles and over 40,000 Soviet troops arrived in Cuba.

On 14 October 1962 a U-2 reconnaissance flight photographed missile launch sites being prepared at San Cristóbal. On 16 October Kennedy and the EXCOMM team — the Executive Committee of the National Security Council — met for the first time. Options: airstrike, ground invasion, blockade, diplomatic pressure. The military leadership (notably General LeMay) wanted an airstrike — almost certainly leading to nuclear retaliation.

On 22 October Kennedy addressed the nation; a "quarantine" — in effect a naval blockade — of Cuba was declared. On 24 October Soviet ships stopped just short of the blockade line. On 27 October, "Black Saturday": a U-2 was shot down over Cuba and Major Anderson killed; American destroyers dropped warning depth charges on Soviet submarine B-59, whose captain Savitsky wanted to launch its nuclear torpedo but was refused by second officer Vasili Arkhipov — a single individual's decision saved humanity.

The crisis was resolved that same night. Through a secret channel between Kennedy and Khrushchev a compromise was reached: the Soviets would withdraw their missiles from Cuba; in return the US would quietly remove the Jupiter missiles from Turkey and publicly pledge not to invade Cuba. The Turkey side of the deal stayed secret for years, leaving the public impression that Khrushchev had backed down — a factor in his removal from Soviet leadership in 1964. After the crisis a Washington-Moscow "hot line" telephone was set up (1963) and the first treaty limiting nuclear testing was signed (1963). On the Eon timeline this is the moment humanity has stood closest to its own end.