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At the age of twelve James Gunn began his filmmaking career with an eight-millimeter camera. His first film featured his brother Sean, now an actor on WB's The Gilmore Girls, being disemboweled by zombies.

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Gunn grew up and attended St. Louis University, where he earned a BA in Psychology. He then attended Columbia University in New York and received his MFA in creative writing.

While at Columbia, he applied for a part-time job filing papers at famed B-movie studios Troma Entertainment, and ended up writing the screenplay for a movie called Tromeo & Juliet instead-he was paid $150 to do so. In 1997, Tromeo became a cult hit, playing in theaters around the world, including over a year of midnight screenings in Los Angeles. Gunn stayed at Troma for two years as Troma's president of production, wrote and directed television segments for the BBC and HBO/Cinemax, and for a time even ran his own television station, Troma's Edge TV, in the Netherlands and Amsterdam. Gunn has also acted in the Troma films Citizen Toxie: The Toxic Avenger 4 and the appropriately entitled Tales from the Crapper.

Gunn left Troma to write and star (along with Rob Lowe, Jamie Kennedy and his own brother, Sean) in the feature film, The Specials, about a group of superheroes on their day off.

Gunn wrote the novel The Toy Collector, released by Bloomsbury Press in 2000, which tells the story of a hospital orderly who sells drugs to finance his escalating toy collecting addiction. He also wrote, with Lloyd Kaufman, the non-fiction book All I Need to Know About Filmmaking I Learned from the Toxic Avenger.

In 2002 the live-action film Scooby-Doo was released into theaters. Gunn wrote the screenplay for the film, the first movie he was involved with that he allowed his mother to see. The film has so far grossed $275 million worldwide.

In addition, Gunn has written and created television pilots for the WB and Fox. He has written Spy vs. Spy for director Jay Roach and The Newlyweds, a romantic comedy, both for the same studio. Upcoming for Gunn is Scooby-Doo 2: Monsters Unleashed, scheduled for a spring 2004 release, on which he served as screenwriter and co-producer.