In 1891, Ben Talbot is attacked by a wolf-like creature. Shakespearean actor Lawrence Talbot returns home after receiving a letter from Ben's fiancée, Gwen Conliffe, informing him of Ben's disappearance. Lawrence reunites with his estranged father, Sir John, who informs him that Ben's body had already been found, mutilated. At a local pub, Lawrence overhears the locals believing it to be a wild animal, but many blame Gypsies who are camped outside the town, while another claims there was a similar murder 25 years earlier, and a werewolf was the suspected killer. Lawrence has flashbacks as he tours his family's home where his mother, Solana, committed suicide when he was a boy. Lawrence saw his father standing over her dead body; afterwards he was sent to Lambeth Hospital in London for a year, having suffered from delusions connected to the event.
Lawrence visits the Gypsies during a full moon. The local townspeople raid the camp to confiscate a dancing bear they believe is the killer, but a werewolf attacks the camp and bites Lawrence before being chased away. A Gypsy woman named Maleva sutures his neck wounds, but another gypsy insists the now-cursed Lawrence should be killed before he kills others. Maleva refuses, saying he is still a man and that only a loved one can release him.
Lawrence recovers unnaturally quickly, and develops heightened vitality and senses. His father's Sikh servant Singh shows Lawrence a set of silver bullets and implies that something monstrous is loose in Blackmoor. Inspector Francis Aberline arrives to investigate the recent killings, and suspects Lawrence is responsible based on his mental history. Fearing for Gwen, Lawrence sends her away. He follows his father to his mother's crypt, where Sir John locks himself in a room alone and gives Lawrence a cryptic warning. Lawrence undergoes a painful transformation into the Wolfman before running off into the woods and killing the hunters stationed there.
The next morning, Aberline and the police arrest Lawrence. Taken back to Lambeth, Lawrence is subjected to torturous, more advanced treatments overseen by Dr. Hoenneger. Sir John visits Lawrence and explains that 25 years ago, in India, he was bitten by a feral boy infected with lycanthropy. Lawrence realizes his father, as a werewolf, killed his mother and brother. Sir John informs him that the moon will be full that night and leaves a razor in case Lawrence contemplates suicide.
By nightfall, Dr. Hoenneger conducts an evening lecture with Lawrence as a case study. Lawrence transforms into the Wolfman, kills Dr. Hoenneger, and goes on a rampage throughout London, with Aberline in pursuit. The next day, Lawrence visits Gwen's antique shop for help. They realize they are falling in love and share a passionate kiss. Aberline arrives and searches the shop, but Lawrence has already escaped to Blackmoor. The Inspector arrives there ahead of him and waits outside Talbot Hall, arming himself and accompanying policemen with silver bullets. As she travels back, Gwen searches for Maleva in the hopes of finding a way to cure Lawrence, but all she receives is the gypsy's blessing.
Lawrence arrives at Talbot Hall and finds the dead bodies of Singh and Constable Carter. He loads a gun with Singh's silver bullets and attempts to shoot his father, but learns that Sir John had removed the powder from the cartridges years ago. The Talbots transform into werewolves and set Talbot Hall on fire as they battle, with the Lawrence Wolfman emerging victorious. Gwen and Aberline arrive; Aberline attempts to shoot the Wolfman, but Gwen stops him, resulting in Aberline being bitten.
The Wolfman pursues Gwen and corners her above a gorge. She pleads with Lawrence, whose consciousness recognizes her. The police and hunters approach, distracting the Wolfman long enough for Gwen to shoot him. Lawrence reverts to human form, thanks Gwen for setting him free and dies in her arms. As Talbot Hall burns, a howl is heard in the distance.
