Initially, Elwin Ransom, the central character, appears to be a typical English figure: a university professor on a walking holiday. However, early in the story, this reluctant hero's character becomes compelling as he fulfills a promise to a distressed mother, despite his understandable hesitation to appear foolish. In all his reactions, Ransom exhibits psychological authenticity: terror upon realizing he is in space; dread of the sorns; near insanity when isolated on Malacandra; an exhilarating and overwhelming curiosity during his first encounter with a hross; sorrow and remorse over Hyoi's death; embarrassment at Weston's foolishness in Oyarsa's presence; and pure, primal joy at returning to Earth. Overall, he is a noble everyman, credible in his thoughts and actions, and admirable in his development.

The other two primary earthmen, Weston and Devine, serve as Ransom's antagonists and are portrayed with varying degrees of depth in the novel. Devine plays a secondary role, depicted as an old schoolmate of Ransom's whose involvement in Weston's schemes is purely for personal gain. Oyarsa describes him as broken, driven solely by greed. In contrast, Weston is far more intricate and, according to Oyarsa, significantly more dangerous. His intelligence and ruthlessness are evident from his first appearance when he assists Devine in kidnapping Ransom. Weston's characteristic rudeness permeates every conversation he engages in throughout the novel.

The most revealing moment for Weston occurs in a scene where he tries to use his anthropological theories to communicate with the assembled Malacandrians at Meldilorn. Unaware of how absurdly humorous he appears, Weston speaks a form of pidgin-Malacandrian, addresses an elderly and sleeping hross, dangles beads, alternates between threats and flattery, and endures fourteen cold dousings due to Oyarsa's belief that such behavior indicates a mental ailment that cold water might cure. Weston's subsequent explanation to Oyarsa about his mission to Malacandra is summarized by Oyarsa as being driven not by love for his fellow humans but by a worship of mankind's lineage. Weston dismisses this analysis as mere twisted logic. Both Weston's and Devine's disregard for others is further highlighted when they leave Ransom asleep in the landed spaceship, an act that was recklessly dangerous for him.

The other notable characters are Malacandrians: the poetic hross, Hyoi; the absent-minded, intellectual sorn, Augray; the froglike, insect-like, sensitive artist, pfifltrigg Kanakaberaka; and the elusive, radiant ruler of the planet, Oyarsa. Through these diverse hnau, or rational beings, Lewis crafts memorable characters that embody the overarching traits of their species, achieving a form of realism through the appropriateness of their language, skills, and interests to their described natures.