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While on an expedition to reach the North Pole, Captain Robert Walton (Aidan Quinn) comes across a man fleeing across the ice, trying to escape whatever is creating a loud moaning in the distance. Walton gives shelter to the man, who introduces himself as Victor Frankenstein (Kenneth Branagh) and who begins to relate to him a terrifying story. As a promising young medical student but devastated by the early death of his mother during childbirth, Victor created a new life by sewing together body parts from various corpses and reanimating them with electricity. His nameless creation (Robert De Niro) escaped from the laboratory but found himself feared and shunned wherever he went. Vowing revenge on his "father", the creature forced Victor to create a female like him, promising to take his "bride" to the far north where they could live together outside of human society. When Victor failed to follow through, however, the monster renewed his revenge by taking the life of Victor's bride, Elizabeth (Helena Bonham Carter).

Mary Shelley's Frankenstein is based on the 1818 novel, Frankenstein; or, The Modern Prometheus, by 19-year-old British author Mary Wollstonecraft Godwin Shelley [1797-1851].

His story completed, Victor closes his eyes and dies. Their ship still stuck in the ice, the captain decides that they will continue heading north, against the wishes of the crew who are on the verge of mutiny. Suddenly, a moan is heard coming from the cabin where Victor lies. The captain and first mate open the door to find Frankenstein's creature sitting at his bedside, weeping. "Why do you weep?", the captain asks. "He was my father," the creature replies. Shortly thereafter, Victor is laid to rest on a pyre. Just as they are about to light it, the ice begins breaking up beneath them, and the crew rush to the safety of their ship. The captain invites the creature to go with them, but he refuses. "I'm done with man," he says. He grabs the torch and swims with it to the ice floe bearing Victor's pyre. While the crew watches, the creature lights the pyre, encompassing both Victor and himself in the flames. In the final scene, the first mate asks, "Where to now, captain?", and the captain replies, "Home."

Stories can have different meanings to different viewers, but the four most commonly mentioned central themes to Frankenstein seem to be: (1) the importance of considering the consequences of one's actions, (2) society's inhumanity towards man, (3) the futility of revenge, and (4) the importance of paternal responsibility. There is also the theme of strange individuals longing for the company of alike others.