Authoress Mary Shelley (Elsa Lanchester) is persuaded by Lord Byron (Gavin Gordon) to continue her story of Frankenstein's creation (Boris Karloff) following his presumed demise in a burning mill. After the parents of the drowned girl discover the Monster had escaped the fire, they fall into his clutches and are murdered. Seeking companionship, the creature rescues a shepherdess from drowning, but he is captured by the villagers. Escaping from the village jail, he terrorizes the countryside, killing several people. The Monster is befriended by a blind hermit (O.P. Heggie) who teaches him to speak. But two hunters arrive and reveal the identity of the creature.
While recuperating from his near-fatal encounter with his creation, Henry Frankenstein (Colin Clive) is visited by his former teacher, Dr. Pretorious (Ernest Thesiger). Pretorious reveals to Henry his experiments in creating life: tiny human beings in glass jars. Eager to create a mate for the Monster, Pretorious persuades Henry to help him by abducting his bride, Elizabeth (Valerie Hobson). After Pretorious' servant, Karl (Dwight Frye), murders a young woman to secure a human heart, the scientists' creation comes to life during a violent electrical storm. But when the moment arrives for the Monster to claim his Mate (Elsa Lanchester), she recoils from him and shrieks in terror. Grief-stricken, the Monster destroys himself and everyone else, after allowing Frankenstein to join Elizabeth in safety.