Dr. Henry Frankenstein (Colin Clive) wants to build a man in his own image, using the body of a dead man. He and his assistant Fritz (Dwight Frye) dig up a freshly buried coffin and steal the body. When they realize the head and the brains of the body are severely damaged, they decide to steal a brain from Dr. Frankenstein’s former teacher Dr. Waldman (Edward van Sloan). When Fritz accidentally drops the glass jar with the label “good brain” on it, on the floor, he decides to take the glass jar with the label “bad brain”. Using some kind of mysterious ray that Dr. Frankenstein discovered, the body is brought to life during a thunderstorm, and the monster of Frankenstein (Boris Karloff) is born.
Later, when Dr. Frankenstein realizes that he has created an aggressive monster, he and Fritz lock the monster up in a cell. When the monster is repeatedly bullied and provoked by Fritz, the monster eventually manages to kill him. When the monster escapes, he meets a little girl playing near the water. The monster and the girl throw flowers in the water. Enjoying the playing, the clumsy monster proceeds to pick up the girl and throw her in the water too. Later we learn that the little girl drowned in the incident, when her father carries her through the streets.
The city’s population propel into an uproar, demanding the death of Frankenstein’s monster. The monster is driven into an old mill, after which the people of the city set the mill on fire.
