Wilfred Glendon (Henry Hull) is a wealthy and world-renowned English botanist who journeys to Tibet in search of the extremely rare selenotropic plant known as mariphasa lupine lumina. While there, he is attacked and bitten by a creature later revealed to be a werewolf, although he succeeds in acquiring a specimen of the mariphasa. Once back home in London he is approached by a fellow botanist, Dr. Yogami (Warner Oland), who claims to have met him in Tibet while also seeking the mariphasa. Yogami warns Glendon that the bite of a werewolf would cause him to become a werewolf as well, adding that the mariphasa is a temporary antidote for the disease.

Glendon does not believe the mysterious Yogami. That is, not until he begins to experience the first pangs of lycanthropy, first when his hand grows fur beneath the rays of his moon lamp (which he is using in an effort to entice the mariphasa to bloom), and later that night during the first full moon. The first time, Glendon is able to use a blossom from the mariphasa to stop his transformation. His wife Lisa (Valerie Hobson) is away at her aunt Ettie's party with her friend, former childhood sweetheart Paul Ames (Lester Matthews), allowing the swiftly transforming Glendon to make his way unhindered to his at-home laboratory, in the hopes of acquiring the mariphasa's flowers to quell his lycanthropy a second time. Unfortunately Dr. Yogami, who is revealed to be a werewolf, sneaks into the lab ahead of his rival and steals the only two blossoms. As the third has not bloomed, Glendon is out of luck.

Driven by an instinctive desire to hunt and kill, he dons his hat and coat and ventures out into the dark city, killing an innocent girl. Burdened by remorse, Glendon begins neglecting Lisa (more so than usual), and makes numerous futile attempts to lock himself up far away from home, including renting a room at an inn. However, whenever he transforms into the werewolf he escapes and kills again. After a time, the third blossom of the mariphasa finally blooms, but much to Glendon's horror, it is stolen by Yogami, sneaking into the lab while Glendon's back is turned. Catching Yogami in the act, Glendon finally realizes that Yogami was the werewolf that attacked him in Tibet. After turning into the werewolf yet again and slaying Yogami, Glendon goes to the house in search of Lisa, for the werewolf instinctively seeks to destroy that which it loves the most.

After attacking Paul on the front lawn of Glendon Manor, but not killing him, Glendon breaks into the house and corners Lisa on the staircase and is about to move in for the kill when Paul's uncle, Col. Sir Thomas Forsythe (Lawrence Grant) of Scotland Yard, arriving with several police officers in tow, shoots Glendon once. As he lies dying at the bottom of the stairs, Glendon, still in werewolf form, speaks: first to thank Col. Forsythe for the merciful bullet, then saying goodbye to Lisa, apologizing that he could not have made her happier. Glendon then dies, reverting to his human form in death.