Teenagers learn a lot of complicated things about growing up. Unfortunately for Jack, becoming "Werewolf by Night" isn't one of those things.
A motorcycle gang follows Lissa Russell to her family's California beach house where brother Jack has been staying since being struck with the curse of the Werewolf. As she runs to the front door, one of the bikers crashes through the large picture windows into the house, knocking Lissa unconscious. From the shadows, the Werewolf leaps onto the gang, who turn and run into the just-arrived police. The Werewolf runs into the woods and later, as he hides near a road, he overhears his step-father, Philip, discussing events with a police officer and another man.
The next morning, Jack awakens and heads to the road to try to hitch a ride. Soon, he is picked up by the very same man who was there with Philip. He introduces himself as Nathan Timly, and tells Jack he can help him. Timly takes Jack to his home where he meets Timly's wife Agatha. Revealing that they have been observing him for some time, Agatha demands information about some book she claims Jack inherited. Ignorant of any such book, and exhausted, Jack passes out.
He later finds himself chained in a cell, terrorized by a slow-witted, deformed brute named Kraig. About to strike Jack with his metal hand, Kraig is stopped by Agatha. When Jack can still offer no information about the book, they leave.
That night, Timly brings Jack some food, but is attacked by the Werewolf. Kraig saves Timly, and the Werewolf is left chined overnight.
The next day, the trio try to bully Jack into revealing the whereabouts of the book known as the Darkhold, but Timly begins to believe Jack truly knows nothing. Kraig, frustrated, strikes Timly and kills him. Jack, handcuffed, takes the opportunity to run from the villa and hides in a workshed.
Having dozed off, Jack awakes in time for the transformation. He breaks his chains and leaves the shed to find and attack Kraig. The two fight brutally, and as Kraig gains the advantage and is about to deliver a crushing blow, lightning strikes him through his steel hand, killing him.
Agatha, having lost everything, returns to her villa, where she suffers a heart attack, knocking over a burning candle as she falls.
The next morning, Jack decides to find this book in the hopes it can cure him.