The story begins with the narrator, a biologist named Edward Prendick, describing how after being shipwrecked and lost at sea for days, he is rescued by a small trading vessel. A man named Montgomery revives him and begins nursing him back to health, with the aid of his small, beastly servant, M’ling. Prendick is repulsed by M’ling’s appearance, though he can’t quite discern why until he notices a greenish gleam in M’ling’s eyes at night, much like that of an animal. Montgomery and M’ling are traveling with a host of caged animals, including many rabbits and a Puma, though they will not tell Prendick what their purpose is. As they near the island that Montgomery and M’ling are traveling to, Captain Davis, owner of the vessel, is set into a drunken rage and abuses M’ling, provoking an altercation between himself and Montgomery. Prendick intervenes and averts a brawl, but earns the captain’s disdain in the process. They reach the island and the captain demands that Prendick leave the ship as well, either putting himself overboard or joining Montgomery and his employer, a scientist named Moreau, who owns the island. Montgomery and Moreau initially refuse to let Prendick join them on the island, but after Prendick is set adrift at sea for the second time by Captain Davis, they take pity on him and bring him to the island.
Prendick is interned in a small room, with a door to Moreau’s laboratory on one side and the island forest on the other. The door to Moreau’s workplace is always locked, and Prendick is impressed by the secrecy of the place. Prendick recognizes the name Moreau, and though it takes him some time to place it, remembers that Moreau had, a decade before, been a subject of great public outrage: the scientist had been discovered to be practicing vivisection on a live dog after the creature escaped his lab, flayed open. The public was horrified, and though Moreau could have repented of his work and maintained his place in society, instead he opted to follow his research and exile himself instead. From his room, Prendick can hear that Moreau has started his work, assumedly vivisection once again, on the Puma, and the screams are so pained that Prendick cannot stand to remain. He leaves his room and wanders into the forest.
While exploring the island, Prendick happens upon a man with the same strangeness of features as M’ling, crouching on all fours and sucking water from a stream, like an animal. The man sees that Prendick has spotted him drinking and acts ashamed. Confused and continuing to wander, Prendick also comes upon a group of individuals who seem human but have strangely swine-like features, and one of them briefly sets upon all fours like an animal. Prendick grows more disturbed and decides to venture back to his room as night begins to fall. On his journey, he realizes that a creature is stalking him. Prendick, panicked, runs and the creature pursues him down to the beach. As the creature closes in, Prendick strikes it in the head with a rock and knocks it unconscious. Although Prendick is too fearful to approach it, he senses that, like the others he has seen, it is some hybridized cross between an animal and a man, presumably a man that has somehow been given beastly qualities. Prendick makes it safely to his room and accosts Montgomery, demanding an explanation. Montgomery will not relent, but does manage to convince Prendick to drink a sleeping draught, explaining that the rest will calm his shattered nerves.
Prendick awakes the following day to find that the door in his room to Moreau’s work place has been left open accidentally. Prendick ventures inward, finding a human-looking being that is mutilated but very much alive, strapped to an operating table. Moreau discovers Prendick in his operating room and forces him out, but Prendick has already seen enough. He feels certain that Moreau is vivisecting human beings to give them animal-like qualities and that he himself will be the next subject strapped to the operating table. Prendick, horrified, fashions a crude weapon from a strap of metal and flees into the jungle.
He meets another creature-like human, the Ape Man, who is enamored of the fact that Prendick has five fingers like he does, and takes him to a community of hovels built by other creaturely humans, the Beast Folk. The Beast Folk all seem able to speak English to varying low degrees and are loosely led by a large, grey-furred humanoid creature they call the Sayer of the Law. The Beast Folk and the Sayer of the Law teach Prendick the Law, a series of religious-sounding incantations that prohibit the Beast Folk from behaving in any way like animals—each prohibition ending with the incantation, “Are we not Men?”—and deifies Moreau as a figure of ultimate authority. Though the Beast Folk are welcoming to Prendick, it seems that they believe he is one of them, augmented as they are. Moreau arrives at the Beast Folk’s community, demanding that they hand over Prendick. Prendick flees again into the forest, this time making his way to the ocean where he intends to commit suicide by drowning rather than let Moreau make him into one of the Beast Folk. However, wading partway in, Prendick realizes that he is cannot bring himself to do it. Moreau and the Beast Folk find him standing in the ocean and Moreau explains that Prendick has misunderstood what is going on—that he is not experimenting on humans at all. As a show of good faith, Moreau gives Prendick a pair of revolvers, managing to convince Prendick to return to his room so Moreau can explain in full.
Sitting down together, Moreau explains to Prendick that he has spent the last decade on this island continuing his research in vivisection, and that the Beast Folk are not humans turned to animals, but animals who have been made into humans—at least partially. Moreau has yet to reshape an animal entirely into a human, which is his ultimate goal, but so far he has been able to reshape animal bodies into humanoid form and alter their brains to allow for greater intelligence, though still quite low compared to an average person. However, Moreau’s creations tend to revert back to their animal nature over time, which is why he taught them the Law to repress their natural instincts. Though Moreau disdains the creatures he has made and often kills the ones who represent the greatest failure to him, Montgomery seems to have a shameful fondness for them, preferring the company of the Beast Folk to the humans he meets in his annual trips to the coast of Chile for supplies. Montgomery himself is an alcoholic, and though kind, seems to Prendick unfit for human society and thus well-suited to his life on the island as Moreau’s assistant.
Days later, Montgomery discovers the remains of a rabbit, eaten presumably by one of the Beast Folk. This is a disturbing find, since the Beast Folk are absolutely forbidden by the Law from eating meat or tasting blood, which could make them revert to their animal instincts. Moreau gathers the Beast Folk together, and they identify the Leopard Man, the creature that had chased Prendick on the beach, as the culprit. The punishment to be meted out is a return to Moreau’s operating table—which the Beast Folk call the House of Pain—but the Leopard Man disobeys and flees instead. The humans and the Beast Folk give chase. Prendick is the first to find the Leopard Man cowering in fear among some bushes, and, pitying him, shoots the creature in the head so that he will not have to undergo more vivisection, which angers Moreau. Prendick suspects that the Leopard Man was not the only member of the Beast Folk behaving like an animal; the Hyena-Swine—the most powerful and fearsome of the Beast Folk—has also been tasting blood, stalking game, and running on all fours.
Six weeks into Prendick’s stay on the island, the Puma that Moreau has been working on breaks free from the operating room and escapes into the jungle with Moreau in pursuit. Moreau catches up to the Puma, who attacks him, and the two end up killing each other. Prendick, Montgomery, and the Beast Folk find the bodies, which causes the Beast Folk to doubt the Law and Moreau’s power that they had once believed in. Prendick, thinking quickly, manages to convince the Beast Folk that Moreau has not truly died, but simply given up his body so that he can watch them from the sky. The Beast Folk are wary of this, but the ruse is enough to maintain the Law for the time being.
Prendick plans to leave the island, but Montgomery, becoming hysterical after Moreau’s death, gets the Beast Folk drunk with him and sets fire to the boats. In the revelry, the Sayer of the Law kills Montgomery and M’ling, leaving Prendick as the last human on the island. At the same time, Moreau’s workplace and the rooms adjacent catch fire by a spilled oil lamp and burn to the ground, leaving Prendick with no place he can lock himself safely away from the Beast Folk. With no other alternatives, Prendick ingratiates himself into the community of the Beast Folk, even as the order and structure of it crumbles.
Over the next ten months, Prendick lives with the Beast Folk and watches as they slowly regress back into their true animal forms. The Dog Man becomes his loyal companion and defender until he is killed by the Hyena-Swine, whom Prendick kills with his revolver. Although Prendick makes several attempts to build a raft, he finds that he is useless as a carpenter. However, a dingy with two corpses, men who died at sea, washes on the beach and Prendick sets out to sea in it himself. After three days, he is rescued by a passing ship and returns to human society after a year on the island of Dr. Moreau.
However, when he returns to England, Prendick finds that he cannot cope with the bustle of cities and the constant presence of other humans, whom he sees a potential animalism in that he fears they will lapse into. Though he understands that this is primarily an illusion, the fear persists, and Prendick withdraws to the countryside for the rest of his life, living as a recluse committed now to studying chemistry and astronomy. As he watches the stars, Prendick reflects that it is in their capacity to wonder at the cosmos that human beings seem most distinguished from animals.