Aziraphale, an angel (originally a guardian of the Eastern Gate of Eden), and Crowley, a demon (originally the serpent who tempted Eve), have lived on Earth since its creation. Over the millennia, they have formed an odd relationship and taken a liking to humanity. One night, the forces of Hell deliver the infant Antichrist to Crowley, with instructions to swap him with the son of an American diplomat stationed in Britain. Crowley realizes this means that the Apocalypse is coming and persuades Aziraphale to help him prevent it. Together, they decide to influence the Antichrist's upbringing by posing as a nanny and a gardener so that the child can never really decide between Good and Evil.
However, due to several misunderstandings at the hospital, the real Antichrist is actually another boy, Adam Young, who grows up unnoticed in idyllic Lower Tadfield, Oxfordshire, together with his three close friends – Pepper, Wensleydale and Brian. As the foretold end of the world nears, Adam begins to unknowingly use his reality-warping powers, changing the world to fit his vision of how things ought to be, such as raising the lost continent of Atlantis after reading about it in a conspiracy theory magazine, summoning UFOs after talking to his friends about aliens, and having the Amazon rainforest reclaim land lost to urban development. In the meantime, the Four Horsemen of the Apocalypse assemble: War (a war correspondent), Famine (a dietician and fast-food tycoon), Pollution (Pestilence having retired after the discovery of penicillin) and Death (a biker).
Aziraphale and Crowley realize their mistake and begin a frantic search for the Antichrist. Also looking for the boy is Anathema Device, a witch who is trying to prevent the Apocalypse as predicted by her ancestor, Agnes Nutter. Agnes' prophecies are perfectly accurate, but many are so cryptic and specific as to be nearly useless, save to the time, place and person they're meant for. Anathema is joined by Newton Pulsifer, sole recruit of the Witchfinder Army (and descendent of Thou-Shall-Not-Commit-Adultery Pulsifer, the Witchfinder who burnt Agnes Nutter at the stake), who has been sent to investigate the strange phenomena around Tadfield by Sergeant Shadwell, the Army's only other member. Everyone, including Shadwell's medium neighbour, Madame Tracy, converges at Tadfield Military Base, where the Four Horsemen are starting a world-ending nuclear war by tampering with the computer systems.
Amid the increasing chaos, Adam is overcome with visions of greatness and attempts to split the world between his gang. When his friends react with horror at what he is becoming, Adam comes to his senses and decides to stop the Apocalypse. He and his friends make their way to the military base and defeat three of the Four Horsemen, with Death accepting defeat and vanishing. A furious Satan starts to ascend to Earth, but Adam, having heard that "his father is coming", twists reality so that his human adoptive father arrives instead, then modifies everyone's memories of recent events.
With Armageddon averted, Crowley and Aziraphale muse that this was God's plan all along and speculate that the real apocalyptic conflict will be between humanity and the combined forces of Heaven and Hell. Madame Tracy marries Sergeant Shadwell, effectively disbanding the Witchfinder Army. Anathema begins a relationship with Newton and receives a second book of Agnes' prophecies, but decides not to open it, and pass it on to their descendants. Finally, Adam uses his powers to evade his father's grounding and watch the circus setting up with his friends.
