The story starts with the philologist Elwin Ransom, some years after his return from Mars at the end of Out of the Silent Planet , receiving a new mission from Oyarsa, the angelic ruler of Mars. After summoning Lewis, the first person narrator, to his country home, Ransom explains to Lewis that he (Ransom) is to travel to Perelandra (Venus), where he is to counter some kind of attack launched by Earth's Black Archon (Satan).
Ransom is transported in a casketlike vessel seemingly made of ice, which contains only himself. He gets Lewis to blindfold him so the sunlight will not blind him once he travels beyond the earth's atmosphere. He does not wear any clothes on the journey as Oyarsa tells him clothes are unnecessary on Venus. He returns to Earth over a year later and is met by Lewis and another friend: the remainder of the story is told from Ransom's point of view, with Lewis acting as interlocutor and occasional commentator.
Ransom arrives in Venus after a journey in which he is surrounded by bright colours; the box dissolves leaving Ransom on what appears to be an oceanic paradise. One day is about 23 Earth hours, in contrast to the (roughly) 24 and 25-hour days of Earth and Mars. The sky is golden but opaque. Hence the sun cannot be seen, daylight is somewhat dimmer than on Earth, and the night is pitch black with no stars visible.
The planet is covered, so far as Ransom can at first see, by a sweet-water ocean, which is dotted with floating rafts of vegetation. These rafts resemble islands, to the extent of having plant and animal life upon them, including a kind of dragon-like creature encountered by Ransom early in his visit. However, as the rafts have no geologic foundations, they are in a constant state of motion. The planet's sole observable geological feature is a mountain called the Fixed Land.
Ransom soon meets the Queen of the planet, whose name is later revealed to be Tinidril; she is a cheerful being who soon accepts him as a friend. Unlike the inhabitants of Mars in Out of the Silent Planet , she resembles a human in physical appearance with the exception of her skin color, green; this is said to be the preferred form assumed by sentient creatures as a result of the manifestation of Maleldil, the second person of God, in human form. She and the King of the planet, who is largely unseen until the end, are the only human inhabitants and are the Eve and Adam of their world. They live on the floating raft-islands and are forbidden to sleep on the "Fixed Land".
The rafts or floating islands are indeed Paradise, not only in the sense that they provide a pleasant and care-free life (until the arrival of Weston) but also in the sense that Ransom is for weeks and months naked in the presence of a beautiful naked woman without once lusting after her or being tempted to seduce her.
The plot thickens when Professor Weston arrives in a spaceship and lands in a part of the ocean quite close to the Fixed Land. He at first announces to Ransom that he is a reformed man, but appears to still be in search of power. Instead of the strictly materialist attitude he displayed when first meeting Ransom, he asserts he had become aware of the existence of spiritual beings and pledges allegiance to what he calls the "Life-Force." Ransom, however, disagrees with Weston's position that the spiritual is inherently good, and indeed Weston soon shows signs of demonic possession.
In this state, Weston (or the demon possessing his body) finds the Queen and tries to tempt her into defying Maleldil's orders by spending a night on the Fixed Land. Ransom, perceiving this, believes that he must act as a counter-tempter. Well versed in the Bible and Christian theology, Ransom realises that if the pristine Queen, who has never heard of Evil, succumbs to the tempter's arguments, the Fall of Man will be re-enacted on Perelandra. He struggles through day after day of lengthy arguments illustrating various approaches to temptation, but the demonic Weston shows super-human brilliance in debate (though when "off-duty" he displays moronic, asinine behaviour and small-minded viciousness) and moreover appears never to need sleep.
With the demonic Weston on the verge of winning, the desperate Ransom hears in the night what he gradually realises is a Divine voice, commanding him to physically attack the Tempter. Ransom is reluctant, and debates with the divine (inner) voice for the entire duration of the night. A curious twist is introduced here; whereas the name "Ransom" is said to be derived from the title "Ranolf's Son", it can also refer to a reward given in exchange for a treasured life. Recalling this, and recalling that his God would (and has) sacrificed Himself in a similar situation, Ransom decides to confront the Tempter outright.
Ransom attacks his opponent bare-handed, using only physical force. Weston's body is unable to withstand this despite the Tempter's superior abilities of rhetoric, and so the Tempter flees. Ultimately Ransom chases him over the ocean, Weston fleeing and Ransom chasing on the backs of giant and friendly fish. During a fleeting truce, the 'real' Weston appears to momentarily re-inhabit his body, and recount his experience of Hell, wherein the damned soul is not consigned to pain or fire, as supposed by popular eschatology, but is absorbed into the Devil, losing all independent existence.
While Ransom is distracted by his horror and his feelings of pity and compassion for Weston, the demon reasserts control of the body (or drops the pretence of being the "real Weston"), surprises Ransom, and tries to drown him. The chase continues into a subterranean cavern, where Ransom seemingly kills Weston's body and, believing his quest to be over, searches for a route to the surface. Weston's body, horribly injured but still animated by the Tempter, follows him. When they meet for the last time in another cavern, Ransom first defeats a purely psychological assault by his enemies, and then hurls a stone at Weston's head. Finally, he consigns the body to volcanic flames.
Returning to the planet's surface after a long travail through the caverns of Perelandra, Ransom recuperates from his injuries, all of which heal fully except for a bite on his heel which he sustained at some point in the battle; this bite continues bleeding for the rest of his time on Perelandra and remains unhealed when he returns to earth. Ransom also carves a memorial inscription for Weston, reasoning that it is only just to commemorate a man whose scientific achievements were of great moment, not least his pioneering of space travel, though he also faithfully records Weston's surrender of his will and reason to the Devil.
Ransom meets the King and Queen together with the Oyéresu of Mars and Venus, the latter of whom transfers its divinely ordained dominion over the planet to the King and Queen. All the characters celebrate the prevention of a second biblical "Fall" and the beginning of a utopian paradise in this new world. The story climaxes with Ransom's vision of the essential truth of life in the Solar System, and possibly of the nature of God: strongly paralleling the journeys of Dante in the Divine Comedy.
His mission on Venus accomplished, he returns, rather reluctantly, to Earth in the same manner in which he made the outward journey; his new mission is to continue the fight against the forces of evil on their own territory.