The novel begins in London, in the ''"year of Our Ford 632"'' (AD 2540 in the Gregorian Calendar). The entire planet is united as The World State, under a peaceful world government established in the aftermath of an apocalyptic global war in the 21st century; a government which has eliminated war, poverty, crime, and unhappiness by creating a homogenous high-tech society across Earth, based on the industrial principles of Henry Ford. Fordism forms the bedrock of the new society, gaining a quasi-religious status and forming the backbone of political and economic ideologies. Society is rigidly divided into five social classes, and all members of society are trained to be good consumers to keep the economy strong. All citizens are expected to be involved socially; spending time alone is discouraged, and sexual promiscuity is the social norm. Recreational drug use has become a pillar of society, and all citizens regularly swallow tablets of soma, a narcotic tranquilizer that makes users mindlessly happy. A significant aspect of the society is the mechanisation of reproduction. Citizens of the World State do not reproduce naturally; people are taught to view natural reproduction as a barbarous and primitive act. Instead, all children are created from embryos grown in factories: production of embryos is planned according to the economic capacity of society. For the embryo, the womb is replaced by an artificial life-support mechanism referred to as a ''bottle''. Significantly, each individual's destiny is determined long before he or she is "decanted."

Huxley reveals the world through the eyes of the main protagonists, Lenina Crowne and Bernard Marx (their names allude to Soviet leader Vladimir Lenin and founder of communism Karl Marx). Lenina, a member of the Beta-Plus caste is a laboratory worker in the Central London Hatchery and Conditioning Centre. She is a personification of the new society, happy and "pneumatic", conformist in her behaviour, fulfilling her function in society, which seems to be to sleep with as many men as possible, but largely incapable of free thought. Government indoctrination is the source of her worldview. Bernard, an Alpha-Plus psychologist serves as an antithesis to her. Despite being a member of the upper caste of Alphas, Bernard is intellectually gifted but physically smaller than is typical for an Alpha. This has caused him to be unhappy with his life and to dislike society. He feels deeply insecure with himself and is something of a joke to members of his own caste and others for his odd physical appearance and rejection of societal norms.

The first half of the novel describes life in the World State, and the personalities of Lenina and Bernard. It also introduces the character of Helmholtz Watson, an Alpha-Plus lecturer at the College of Emotional Engineering (Department of Writing). While Bernard's physical defects had isolated him from society, Helmholtz is isolated by his mental and physical excess. This isolation brings Bernard and Helmholtz together and they remain friends throughout the story. Bernard's unacceptable behaviour lands him in trouble with his boss, the Director of Hatcheries and Conditioning. But nevertheless, Bernard secures his permission to visit the Malpais Savage reservation in New Mexico to where he takes Lenina on a date.

The second half of the novel begins with the visit to the Malpais Savage Reservation in New Mexico, where they see an ancient society that has been fenced off and ignored by The World State. In the reservation, the two encounter Linda, a woman from The World State who, through an accident, came to live as a savage in Malpais, having given birth to a son named John, the novel's main protagonist. While Lenina is disgusted and horrified by the dirty, neglected and viviparous society of Malpais, Bernard is fascinated by it and by John, who grew up with the lifestyle of the Zuni Native American tribe and a religion that is a blend of Zuni and Christian beliefs. However, he is also influenced by his mother's education (she taught him to read) and by his discovery of the works of William Shakespeare, unknown in The World State. Like Bernard, John is an outcast in his own society and is eager to see the world outside of Malpais. Bernard agrees to take Linda and John back to London, where he manipulates society's fascination with them to boost his own social position.

The culture shock which results when the "savage" is brought into the society of the "Brave New World", as he initially calls it, provides a vehicle for Huxley to contrast the values of The World State society with our own and point out the Brave New World society's major flaws. The key moral point of the book revolves around two diametrically opposing problems. The first, and most obvious, is that in order to ensure continuous and universal happiness, society has to be manipulated, freedom of choice and expression curtailed, and intellectual pursuits and emotional expression inhibited. Citizens are happy, but John the Savage considers this happiness to be artificial and "soulless."

John, who has fallen in love with Lenina, is appalled by the World State and Lenina's promiscuity and willingness to sleep with him without vows. While in London, John meets and quickly becomes friends with Helmholtz Watson. They meet often to discuss writing, especially that of Shakespeare. When his mother Linda dies, John is unable to understand society's reaction to death and reacts violently by attempting to "free" a group of Delta caste menial staff members at the hospital by throwing their daily soma ration out the window. The result is a near riot, to which Bernard and Helmholtz arrive in an attempt to rescue John. Unfortunately the police arrive at the melee and after subduing the crowd with vaporized soma and hypnotic music, they quickly take all three into State custody.

This leads to a confrontation between the three and Mustapha Mond, the Resident World Controller for Western Europe. The heated argument between Mustapha and John ultimately leads to the decision that John will not be set free because Mustapha considers him an ongoing experiment. Bernard and Helmholtz, in a twist of fate, are sent to live in the Falkland Islands, one of several island colonies reserved for exiled citizens of the World State who can no longer be trusted to live in global society, where Helmholtz can become a serious writer and Bernard can live out his life in peace and solitude. John attempts to isolate himself from society on the outskirts of London; however, he is unable to live without lusting for Lenina and constantly punishes himself physically and mentally. This causes him to be constantly harassed by inquisitive sightseers. At the very end of the novel, John attacks Lenina and succumbs to an orgy of drugs and sex. In the morning John, horrified by what he has done to Lenina and disgusted by himself, commits suicide in grief, mirroring Shakespeare's Othello.