Humankind sends its first human expedition to Mars. The spaceship's crew arrives on the planet and are never heard from again. Twenty-five years later, another mission is sent, and the child of two of the first ship's crewmembers, who has been born on Mars and raised by the peculiar Martian race, is discovered and brought back to Earth. Because of various legal precedents, Valentine Michael Smith, the Man from Mars, is the inheritor to a vast fortune, and because of another precedent known as the Larkin Decision, Mike has a claim to legal ownership of the planet Mars. Therefore he has the potential to be massively influential in matters of Earth politics, and he is kept under close guard at a hospital by the leader of Earth's government, Secretary General Joseph Douglas. In the hospital, Mike slowly teaches his body to adapt to the Earth's atmosphere and he begins learning Earth culture and language, which differ enormously from Martian ways of thought.
An ambitious reporter, Ben Caxton, believes that Douglas is using Mike as a pawn in his own political power games and may be planning to kill him. Ben enlists his friend and old flame, Jill Boardman, a nurse at the hospital, to help him spy on Mike's treatment at the hospital. When Ben lets on to the authorities that he has a notion of their plans, they kidnap him. Jill sneaks Mike out of the hospital. When police officers try to kidnap them as well, Mike makes the officers disappear from existence—one of many psychic powers Mike has learned on Mars.
Jill takes Mike to the only man she believes can help them, Jubal Harshaw, a famous doctor, lawyer, writer, and general cultural phenomenon. Jubal lives in a large house with three beautiful secretaries (Anne, Miriam, and Dorcas) and two male assistants (Duke and Larry). Jubal agrees to help protect Jill and Mike from the authorities. Mike learns about Earth culture at Jubal's estate, reading everything in Jubal's library and becoming fascinated with Earth religions. The police eventually discover Mike's whereabouts and come to arrest Jubal and his coterie, but at the last moment, Jubal is able to get through to Douglas personally and convince him to call off the police. Jubal also gets Douglas to rescue Ben from police captivity. Through legalistic maneuvering and rhetorical brinksmanship, Jubal is able to defuse Mike's political importance, arguing that Mike cannot be the legal owner of Mars since the Martian race inhabited it long before Mike was born. Jubal makes Douglas an ally by convincing him to become overseer of Mike's vast personal fortune.
Following up on Mike's fascination with religion, he and Jubal and Jill go to visit the headquarters of a religious group called the Fosterites. The Fosterites have aggressively built a massive following, in part by enlisting entertainers, such as football players and strippers, to deliver their message, and incorporating vices like gambling into their organization. The Fosterite Supreme Bishop, Digby, hopes to enlist Mike to lend his celebrity to their cause, but, when they are alone in a room together, a conflict arises and Mike makes Digby disappear.
Mike contemplates deeply on his action, and eventually comes to feel that he had made the best decision possible in a difficult moment. Mike is imbued with new self-confidence, and decides to set out and see the world. With Jill as his companion, Mike travels to various cities incognito, experiencing Earth culture. They develop a magician's act that exhibits Mike's powers and join a carnival, but despite Mike's amazing abilities, he lacks a sense of showmanship, and they are fired. A Fosterite tattooed lady in the carnival, Patty Paiwonski, goes to visit them at their hotel room, hoping to convert them before they leave. Mike reveals to her that he is the Man from Mars, and reveals his powers. Patty decides that Mike is a new prophet sent to Earth, as powerful as Foster himself.
Jill starts to learn the Martian language and some of Mike's psychic powers as they continue to travel together. Mike comes to grasp many human concepts that have eluded his understanding, such as desire and humor. Finally he believes he understands Earth culture and is ready to help people get past the petty fears and jealousies that enslave them. He founds a church, called the Church of All Worlds, which uses flashy salesman-like techniques much as the Fosterites do to attract new members. The church grows in prominence, and a core group of followers—the "ninth circle"—live together communally, where they all work at learning Martian and developing psychic powers. They rarely wear clothing and engage in group sex and partner swapping in a manner disconcerting to outsiders. Ben goes to visit them and is deeply unnerved by their cultish behavior and open sexuality, but soon enough he has overcome his fears and joined them as well.
Jubal—who has come to think of Mike as a son—worries about the increasing persecution Mike is facing, and wonders if Mike is not encouraging this persecution. When Mike's temple is burned down, Jubal rushes to see him. Though Jubal loves Mike, he has resisted visiting Mike's church. Jubal's philosophies are all deeply individualist, and Jubal, like Ben, is unnerved by the cultism of Mike's operation. But Jubal is comforted among Mike's flock, who all treat Jubal as a formidable father figure.
Mike wonders aloud to Jubal if his attempts to help humanity are fruitless, if his message is being lost because of an inherent need in humans to create unhappiness and strife for themselves. Jubal encourages Mike to stay true to his beliefs and ideas. An angry mob gathers outside the hotel where they are staying, and, in true showman fashion, Mike presents himself to the mob, naked and defenseless. They murder him and he ascends to Heaven where he becomes an archangel alongside such other self-made prophets as Foster and Digby. Jubal and Mike's followers forge ahead with Mike's work on Earth.