Phil Jenkins Jeff Denton is the new sheriff of Walworth County, Wisconsin, recently transferred from Chicago. Phil is dating Kelly Sarah Lieving, the owner of a local tavern called Kelly's Roadhouse, and is assisted in his duties by Deputies Pamela Fitske Noel Thurman and Dennis Snarski Matt Kawczynski. When people and animals start turning up dead, all of them ripped apart and eaten, rumors swirl about the return of the Beast of Bray Road, a mythical wolf-like creature whose legend dates back to the 19th century. The gossip attracts Quinn McKenzie Thomas Downey, a cryptozoologist who inserts himself into the investigation, much to Phil's annoyance.
As the bodies pile up, mounting evidence, such as the teeth marks on a victim's bones and DNA analysis of fur found at attack sites, suggests the predator is really a werewolf; this is confirmed by dashcam footage recovered from Dennis's car after he is killed by the Beast Joel Ezra Hebner. Billy Loubes [Dan Tana], the best local hunter and the bereaved younger brother of two victims, agrees to allow Phil, Quinn, and Pamela access to his vast arsenal of firearms in exchange for letting him help hunt the Beast. The quartet coats their bullets in silver (the only substance that can nullify a werewolf's regenerative powers) and brew a serum out of nightshade and Wolf's bane, described as > the Ebola virus for werewolves by Quinn, to tip the odds in their favor.
The Beast wounds Quinn and bites Billy, but before it can finish either of them off, it is shot in the leg by Phil, who pursues it to the Roadhouse. Phil realizes that Kelly is the Beast when he sees her wounded leg; Kelly reveals that she was bitten by another werewolf, implied to be the actual Beast of Bray Road, and explains that, while she initially only transformed during the full moon, she eventually mastered the change, though she admits that lately she has "lost control of it." Kelly partially transforms and bites Phil, who injects her with Quinn's serum, forcing her back into her human form while he regroups with Pamela. To buy time while the serum wears off, Kelly tricks Pamela into shooting Phil, then kills Pamela. Phil is saved by his bulletproof vest, and as Kelly fully transforms, a pair of motorists pull up to the Roadhouse. While Kelly is distracted murdering the men, a recovered Billy sets her on fire before he and Phil finish her off by shooting her, with Billy snarking, "Silver bullets, bitch."
The film ends with Phil and Billy, now cursed with lycanthropy, temporarily sequestering themselves in the mountains after being supplied with more of the anti-werewolf serum by Quinn.