Dougherty made his directorial and writing debut with the short film Season’s Greetings, which was released in 1996.

Dougherty went on to co-write several screenplays, including Bryan Singer’s superhero sequel film X2, which was released in 2003. He also co-wrote the screenplay for the 2005 supernatural horror film Urban Legends: Bloody Mary. Dougherty re-teamed with Singer, co-writing the story and screenplay for the superhero film Superman Returns, which was released in 2006.

Dougherty made his feature length directorial debut with the cult horror anthology film Trick ‘r Treat. The film was based on his own script, and was produced by Singer. It played at several film festivals, before being released on DVD on October 6, 2009 in the US and Canada. It received acclaim and went on to gain a cult following in subsequent years. The short film Season’s Greetings, which was the precursor to Trick ‘r Treat, was released as a DVD extra and was aired on FEARnet in October 2013 as part of a 24-hour Trick ‘r Treat marathon on Halloween.

In December 2014, he began work on the Christmas horror film Krampus, which was released to moderate critical and commercial success in December 2015. He also co-wrote the story for the film X-Men: Apocalypse (2016), with Singer, Dan Harris and Simon Kinberg, with Singer once again as director. Dougherty directed the science fiction sequel Godzilla: King of the Monsters, for which he wrote the script with Zach Shields, from a story by himself, Shields, and Max Borenstein. The film was released in 2019, to mixed reviews and grossed $386 million worldwide.

In 2015, with Todd Casey, Zach Shields and Marc Andeyko, Dougherty co-wrote and created a comic book tie in to Trick ‘r Treat, titled Trick ‘r Treat: Days of the Dead. It featured four new short stories, spanning centuries, depicting a variety of characters and cultures, going back to the holiday’s roots in ancient Ireland. Later that year, with Casey, Zach and Laura Shields, Dougherty published a tie-in to Krampus, titled Krampus: Shadows of Saint Nicholas. It features three stories which expand the mythology of the Krampus.

In April 2020, HBO was announced to be developing a Hellraiser television series that would serve as “an elevated continuation and expansion” of its mythology, with Mark Verheiden and Dougherty writing and David Gordon Green directing several episodes. The three will executive produce with Danny McBride, Jody Hill, Brandon James and Roy Lee of Vertigo Entertainment.