Ransom, a college professor in philology, is on a walking tour in England when he is unable to find a hotel for the night. Stopping off at a farmhouse, he is asked by the woman living there if can check on her son, who works for a scientist at a nearby residence. Ransom, hoping to find a place to stay, agrees to help her. Upon arriving Ransom finds the men harassing her son. After breaking up the disagreement, he realizes he knows one of the two men (Devine) from his days at school (though he does not have fond memories of him). Feigning hospitality, Devine offers Ransom a drugged glass of water. When Ransom wakes, he finds himself in a spaceship with Weston and Devine travelling to the planet of Malacandra (which we later learn is Mars). During the multi-month voyage, Ransom is unable to gather sufficient information about why they are travelling to another planet, but at one point he does overhear that he is being brought along so that he can be offered as a sacrifice to the local residents. Eventually, they arrive on the planet, which is covered in a pink-white weed, tall thin blue "trees", and blue water. Soon they see some natives (Sorns), which are tall, elongated humanoid creatures. Afraid that these are the natives he is going to be sacrificed to, Ransom takes advantage of the chaos of their arrival (and the arrival of a monstrous water creature) to flee the two men.

Not long after fleeing the sorns and the two men, Ransom runs into another native, a Hrossa named Hyoi. Realizing the creature is speaking a language, Ransom initiates contact with Hyoi. The two become friends, and Hyoi begins teaching the Malacandra language to Ransom. Several months pass during which Ransom becomes increasingly fluent in their language, and learns much about their culture. Several important things he learns about are the hnakra (the monster that attacked the humans upon their arrival), the eldila (an angelic like creature that lives in an alternate dimension, and can be seen only vaguely by humans), Oyarsa (the eldil that is the leader of Malacandra who has sent for Ransom), and that there are three hnau (sentient beings) on Malacandra - the hrossa, sorns, and pfifltriggi (a frog-like species that is known for its creations, stone working, and mining). He also learns the concept of "bent" - basically what happens when a creature becomes evil, or does not follow the path of Maleldil (God in the space trilogy theology). When the hrossa learn that there is a hnakra that attacked Ransom, a hunt for it begins. Ransom joins Hyoi and another hrossa on the hunt and they are successful. Immediately after, Weston and Devine shoot Hyoi, killing him. Ransom flees at the bidding of the other hrossa to finally seek out Oyarsa. Travelling over a mountain, Ransom meets Augray, a Sorn who helps him take the remainder of the trip to Meldilorn (the land where Oyarsa lives). Ransom meets with Oyarsa shortly after arriving in Meldilorn, who we learn was all along simply trying to meet with someone from Thulcandra (Earth), so he could learn what is happening on the Silent Planet. Earth is called that because its Oyarsa became bent, and was cut off from the rest of the eldila. His meeting is interrupted by the arrival of Weston and Devine. Weston, at first unwilling to admit Oyarsa exists, attempts to frighten the natives into freeing him by threatening to kill them and by espousing his dream of spreading man to all planets so it can survive eternally as a species. Oyarsa, unconvinced, says they must leave immediately and in 90 days their ship will be destroyed regardless of where it is. Ransom finishes telling Oyarsa of what is occurring on Earth, and learns that great events are in the works in the universe. Ransom decides to return to Earth with Weston and Devine, though he knows he may not survive. They do survive (by travelling close to the sun in order to cut the length of the trip) and we learn at the end that Lewis wrote the book as a fiction to get the word out, but in fact the events actually did occur to a colleague of his.