The novel begins with explorer Robert Walton looking for a new passage from Russia to the Pacific Ocean via the Arctic Ocean. After weeks as sea, the crew of Walton's ship finds an emaciated man, Victor Frankenstein, floating on an ice flow near death. In Walton's series of letters to his sister in England, he retells Victor's tragic story.
Growing up in Geneva, Switzerland, Victor is a precocious child, quick to learn all new subjects. He is raised with Elizabeth, an orphan adopted by his family. Victor delights in the sciences and vows to someday study science. Victor prepares to leave for his studies at the University of Ingolstadt, when his mother and Elizabeth become ill with scarlet fever. Caroline dies from the disease, and Elizabeth is nursed back to health.
At the university, Victor meets his professors M. Krempe and M. Waldman. For two years, Victor becomes very involved with his studies, even impressing his teachers and fellow students. He devises a plan to re-create and reanimate a dead body. He uses a combination of chemistry, alchemy, and electricity to make his ambition a reality.
After bringing the creature to life, Victor feels guilty that he has brought a new life into the world with no provisions for taking care of the "monster." He runs away in fear and disgust from his creation and his conscience. The monster wanders the countryside while Victor seeks solace in a tavern near the university. Henry Clerval appears to save Victor and restore him to health.
Alphonse writes to Victor telling him to come home immediately since an unknown assailant murdered his youngest brother, William, by strangulation. Justine Moritz, their housekeeper, is falsely accused of the murder of William, and she goes to the gallows willingly. Victor knows who the killer is but cannot tell his family or the police. He journeys out of Geneva to refresh his tortured soul and visits Mount Montanvert when he sees the monster coming to confront his maker with a proposition — "make me a mate of my own." Victor refuses, and the monster asks that his part of the story be heard. The pair retreats to a small hut on the mountain where the monster tells his story.
The monster has taught himself to read and understand language so that he can follow the lives of his "adopted" family, the De Laceys. While the monster wanders the woods, he comes upon a jacket with a notebook and letters that were lost by Victor. From the notes, the monster learns of his creation. He has endured rejection by mankind, but he has not retaliated upon mankind in general for his misfortune. Instead, he has decided to take revenge on his creator's family to avenge the injury and sorrow he endures from others.
Victor refuses to make a second monster, but is convinced when the monster assures Victor that he will leave Europe and move to South America. Victor agrees to begin work on a second creation and makes plans to go to England and Scotland, with Henry Clerval, to begin his secret work. Before he leaves Geneva, Victor agrees to marry Elizabeth immediately upon his return from the British Isles. Victor takes up residence in the Orkney Islands, off the coast of Scotland. Victor destroys his project and goes out to sea to dispose of the remains. The monster vows revenge on Victor not upholding his end of their bargain.
While at sea, Victor's boat is blown off course by a sudden storm, and he ends up in Ireland. Henry Clerval's body has washed up on the shores of Ireland, and Victor is set to stand trial for murder. Fortunately, Mr. Kirwin, a local magistrate, intercedes on Victor's behalf and pleads his case before a court, which then finds Victor innocent of the crime. Victor is miserable knowing he has caused the deaths of so many, but recovers enough to finalize the plans for his marriage to Elizabeth.
With a wedding date set, Victor torments himself with the thought of the monster's threat to be with him on his wedding night. The wedding goes off as planned. While Victor makes sure he covers all possible entrances that the monster could use to get into the wedding chamber, the monster steals into Elizabeth's room and strangles her.
Victor now wants revenge and chases the monster through Europe and Russia. Victor nearly catches the monster near the Arctic Circle when Robert Walton discovers him. Victor, now near death, is taken aboard Walton's ship to recover from exhaustion and exposure.
The monster appears out of the mists and ice to visit his foe one last time. The monster enters the cabin of the ship and tells Walton his side of the story. Victor dies, and the monster tells Walton that he will burn his own funeral pyre. The monster then disappears in the waves and darkness, never to be seen again.