• Christopher Abbott as Blake Lovell
• Julia Garner as Charlotte Lovell, Blake's wife
• Matilda Firth as Ginger Lovell, Blake and Charlotte's daughter
• Sam Jaeger as Grady Lovell, Blake's estranged father, Ginger's grandfather and Charlotte's father-in-law
• Benedict Hardie as Derek Kiel
• Leigh Whannell as Dan Kiel (voice)
• Milo Cawthorne as Man
• Rob MacBride as SFPD

In July 2014, Universal Pictures announced its plan for a shared cinematic franchise, later dubbed Dark Universe, centered on their Universal Monsters library — which was to include The Wolf Man. In November 2014, Aaron Guzikowski was confirmed to be writing the reboot of Universal's The Wolf Man. In June 2016, Deadline Hollywood reported on rumors that Dwayne Johnson was considered for the titular role. In October, David Callaham was hired to rewrite the script. In 2017, The Mummy was released as the first film in the Dark Universe; its launch was both a critical and commercial failure and resulted in Universal deciding to shift its focus on individual storytelling and move away from the shared universe concept with the cancelation of The Wolf Man and other films in development.

Reporter Justin Kroll said the critical and commercial success of Leigh Whannell's The Invisible Man for Universal "scrap[ped] the universe concept" and loosened restrictions for the talent in front and behind the camera, allowing them to decide how they wanted to execute their films in terms of budget and MPAA rating and invite "big name talent" to pitch their ideas. By early 2020, Universal had been hearing project ideas for a year and a half from filmmakers seeking to develop characters in the franchise. These meetings included Ryan Gosling's pitch to remake The Wolf Man and star in it, with Lauren Schuker Blum and Rebecca Angelo writing a screenplay described as tonally similar to Nightcrawler (2014). Around this time, make-up artist Mike Marino molded an early version of the werewolf.

Several filmmakers were considered to direct, including Cory Finley, whose film Thoroughbreds (2017) was reportedly well liked by Universal, and Whannell, who was advised by Jason Blum of Blumhouse Productions (producer of several of his projects, including The Invisible Man) to reconsider after initially declining. (In February 2020, Whanell had mentioned his interest in making a werewolf film during a press interview for The Invisible Man. ) In July 2020, Whannell entered negotiations to write a film treatment and direct. He and his wife Corbett Tuck co-wrote the first draft of their version by pulling from the feeling of confinement and isolation caused by the COVID-19 pandemic to touch on the inevitability of illness and death, setting the story primarily in one location to make the drama "intimate", and drawing from themes of parenting and marriage. The disease that the main character contracts in the film is meant to resemble neurodegenerative diseases like ALS, which killed a close friend of Whannell's; a deleted scene involved Blake's ALS-stricken mother.
After Whannell left the project due to scheduling conflicts, Derek Cianfrance entered negotiations to write and direct in October 2021, having directed Gosling in Blue Valentine (2010) and The Place Beyond the Pines (2012). The film was officially green lit around …

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In August 2024, during Universal's Halloween Horror Nights in Orlando, a booth revealed the film's logo and teaser image, and on September 4, an actor took the stage for a photo-op performing as the film's werewolf. The werewolf design—a creature with a "balding head", "long white hair on the back of his head and as facial hair", "long, bony fingers", and "sharp teeth"—drew divisive reactions from online users and journalists. On September 6, Universal released a teaser trailer, poster, and synopsis. Hannah Shaw-Williams of /Film suggested that the timing of the teaser's release was "damage control" over the poorly-received werewolf design, noting the absence of the titular creature in the teaser. Whannell described the design reveal as a "debacle", as Universal did it without discussing it with him or the film's make-up artist Arjen Tuiten; he unsuccessfully tried stopping it by calling Jason Blum and later retorted that it was "like judging the Freddy Krueger makeup by a costume at Spirit Halloween." Social media analytics firm RelishMix reported that online marketing led to 136.5 million interactions, 50% behind the average for a wide horror release. Summarizing word of mouth from audiences, it wrote, "Mixed negative-leaning chatter on Wolf Man finds some viewers taking umbrage with the look of the film, from the cinematography to the design of the titular creature."