In 1891, Ben Talbot (Simon Merrells) is confronted by a superhuman wolf-like creature in the Blackmoor woods. He tries to escape, but is mauled and killed by the beast.
Gwen Conliffe (Emily Blunt), Ben's fiancée, has contacted his brother, Lawrence Talbot (Benicio del Toro), the world-renowned Shakespearean actor, saying that Ben disappeared a month ago. Lawrence leaves his theater tour to return to his family's estate in Blackmoor where he has an uneasy reunion with his esstranged father, Sir John (Anthony Hopkins). Later, it is revealed that Lawrence's mother, Solana (Christina Contes), had committed suicide when he was a boy. Lawrence saw his father standing over her dead body, after which, Sir John sent his young son to an insane asylum in London, ostensibly for suffering delusions.
Ben's body, found the day before, has been stored at a slaughterhouse. When Lawrence views his brother's remains, he is horrified—Ben has been viciously mauled. Among Ben's personal effects is a medallion embossed with a monk encircled by three wolves that Ben apparently purchased from gypsies. Later, at the local pub, Lawrence overhears the locals discussing the killing. Many blame the gypsies who are camped outside the town, while another patron claims there was a similar murder several decades earlier, and a werewolf was the suspected killer.