At the front door of a house in the country, Ransom hears shouting and struggling inside. When he hurries around back, he sees Weston and Devine trying to force Harry, a dull-witted young man, to enter a structure on the property against his will. Ransom intervenes, and Devine sees him as a better prospect than Harry for what he and Weston have in mind. With Weston's grudging consent, Devine offers Ransom a drink and accommodations for the night.
After enjoying what he thinks is a glass of water, Ransom realizes that he has been drugged. He tries to escape but is subdued by Weston and Devine. When he regains consciousness he finds himself in a metallic spherical spacecraft en route to a planet called Malacandra. The wonder and excitement of such a prospect relieves his anguish at being kidnapped, but Ransom is put on his guard when he overhears Weston and Devine deliberating whether they will again drug him or keep him conscious when they turn him over to the inhabitants of Malacandra, the sorns , as a sacrifice. Ransom is put to work as cook and scullion, but appropriates a knife and plans to escape when he gets the chance.
Soon after the three land on the strange planet, Ransom gets his chance to run off into the unknown landscape, just after he sees the Sorns—tall alien creatures who terrify him. Ransom wanders around, finding many differences between Earth and Malacandra, in that all the lakes, streams, and rivers are warm; the gravity is significantly less; and the plants and mountains are strangely tall and thin.
Ransom later meets a civilized native of Malacandra, a hross named Hyoi, a tall, thin, and furry creature. He becomes a guest for several months in Hyoi's village, where he uses his philological skills to learn the language of the hrossa and also learns their culture. In the process he discovers that gold, known to the hrossa as "sun's blood", is plentiful on Malacandra, and thus is able to discern Devine's motivation for making the voyage. Weston's motives are shown to be more complex; he is bent on expanding humanity through the universe, abandoning each planet and star system as it becomes uninhabitable.
The hrossa honour Ransom greatly by asking him to join them in a hunt for a hnakra (plural hnéraki ), a fierce water-creature which seems to be the only dangerous predator on the planet, resembling both a shark and a crocodile. While hunting, Ransom and his hrossa companions are told by an eldil , an almost invisible creature reminiscent of a spirit or deva, that Ransom must go to meet Oyarsa, the eldil who is ruler of the planet—and indeed that he already should have done so. He hesitates to respond to the summons, as he wishes to proceed with the hunt. Hyoi, after killing the hnakra with Ransom's help, is shot dead by Devine and Weston, who are seeking Ransom in order to take him prisoner and hand him over to the séroni. Ransom is told by Hyoi's friend (another hross named Whin) that this is the consequence of disobeying Oyarsa, and that Ransom must now cross the mountains to escape Weston and Devine and fulfil his orders. On his journey, Ransom finally meets a sorn, as he long feared he might. He finds, however, that the séroni are peaceful and kindly. Augray (the sorn ) explains to him the nature of Oyarsa's body, and that of all eldila. The next day, carrying the human on his shoulders, Augray takes Ransom to Oyarsa.
After a stop at the dwelling place of an esteemed sorn scientist, wherein Ransom is questioned thoroughly regarding all manner of facts about Earth, Ransom finally makes it to Meldilorn, the home of Oyarsa. In Meldilorn, Ransom meets a pfifltrigg who tells him of the beautiful houses and artwork his race make in their native forests. Ransom then is led to Oyarsa and a long-awaited conversation begins. In the course of this conversation it is explained that there are Oyéresu (the plural) for each of the planets in our solar system; in the four inner planets, which have organic life (intelligent and non-intelligent), the local Oyarsa is responsible for that life. The ruler of Earth (Thulcandra, "the silent planet"), has turned evil (become "bent") and has been restricted to Thulcandra, after "great war," by the Oyéresu and the authority of Maleldil, the ruler of the universe. Ransom is ashamed at how little he can tell Oyarsa about Earth and how foolish he and other humans seem to Oyarsa. While the two are talking, Devine and Weston are brought in guarded by hrossa, because they have killed three of that race. Oyarsa then directs a pfifltrigg to "scatter the movements that were" the bodies of Hyoi and the two other hrossa, using a small, crystalline instrument; once touched with this instrument, the bodies vanish. Weston makes a long speech justifying his proposed invasion of Malacandra on "progressive" and evolutionary grounds, which Ransom attempts to translate into Malacandrian, thus laying bare the brutality and crudity of Weston's ambitions.
Oyarsa listens carefully to Weston's speech and acknowledges that the scientist is acting out of a sense of duty to his species, and not mere greed. This renders him more mercifully disposed towards the scientist, who accepts that he may die while giving Man the means to continue. However, on closer examination Oyarsa points out that Weston's loyalty is not to Man's mind - or he would equally value the intelligent alien minds already inhabiting Malacandra, instead of seeking to displace them in favour of humanity; nor to Man's body - since, as Weston is well aware of and at ease with, Man's physical form will alter over time, and indeed would have to in order to adapt to Weston's programme of space exploration and colonisation. It seems then that Weston is loyal only to "the seed" - Man's genome - which he seeks to propagate. When Oyarsa questions why this is an intelligible motivation for action, Weston's eloquence fails him and he can only articulate that if Oyarsa does not understand Man's basic loyalty to Man then he, Weston, cannot possibly instruct him.
Oyarsa, passing judgment, tells Weston and Devine that he would not tolerate the presence of such creatures, but lets them leave the planet immediately, albeit under very unfavourable orbital conditions. Oyarsa offers Ransom the option of staying on Malacandra, but Ransom decides he does not belong there, perhaps because he feels himself unworthy and perhaps because he yearns to be back among the human beings of Earth. Oyarsa gives the men ninety days' worth of air and other supplies, telling the Thulcandrians that after ninety days, the ship will disintegrate—so that whether they make it back to Earth or not (which is unlikely given the orbital conditions), they will never return to Malacandra. Weston and Devine do not further harm Ransom, focussing their attention on the perilous journey home. Oyarsa had promised Ransom that the eldila of "deep heaven" would watch over and protect him against any attacks from the other two Thulcandrians, who might seek to kill him as a way of economizing their air and food supplies; at times, Ransom is conscious of benevolent presences within the spaceship—the eldila . After a difficult return journey, the space-ship makes it back to Earth, and is shortly "unbodied" according to Oyarsa's will.
Ransom himself half-doubts whether all that happened was true, and he realizes that others will be even less inclined to believe it if he should speak of it. However, the author (Lewis, appearing as a character) who did not previously know of Ransom's adventure, fortuitously writes to Ransom asking whether he has heard of the medieval Latin word "Oyarses" and knows what it meant. This prompts Ransom to let Lewis in on the secret. Ransom then dedicates himself to the mission that Oyarsa gave him before he left Malacandra: stopping Weston from further evil. Ransom and Lewis then collaborate—in the story, not in real life—to compose and publish Out of the Silent Planet under the guise of fiction. They realize that only a few readers will recognize their story as describing "real" events, but since they anticipate that further conflict with Weston or the Bent Oyarsa of Earth will be forthcoming, they also desire simply to familiarize many readers with the ideas contained therein.