Stuart Gordon started his film directing career in 1985. After graduating from Lane Technical High School, Gordon worked as a commercial artist apprentice prior to enrolling at the University of Wisconsin in Madison. Unable to get into the film classes, he enrolled in an acting class and ended up majoring in theater. In 1968, he directed a psychedelic adaptation of Peter Pan as a political satire. He was arrested on obscenity charges and Gordon dropped out of the university. He and his wife Carolyn formed the Organic Theater and moved the group to Chicago.

The Organic performed their work on and off-Broadway, in Los Angeles, and toured Europe. Among their productions were the world premiere of David Mamet's "Sexual Perversity in Chicago," which launched Mamet's playwriting career, the improv-based comedy "Bleacher Bums," which ran for over ten years in Los Angeles, and the hospital comedy E/R (1984), which became a TV series produced by Norman Lear.

He joined with Brian Yuzna and Charles Band's Empire Pictures to create the company's first major hit, Re-Animator (1985), based on the story by H.P. Lovecraft, which won a Critics' Prize at the Cannes Film Festival. Gordon then helmed another Lovecraft adaptation From Beyond (1986) and tackled the murderous Dolls (1986) followed by Robot Jox (1989). Gordon co-created the story for Honey, I Shrunk the Kids (1989) a major hit for Disney. The same year, he directed the remake and more graphic version of The Pit and the Pendulum (1991). Other works include Fortress (1992), and the screenplay for The Dentist (1996) and Body Snatchers (1993), which he co-wrote with long-time writing partner Dennis Paoli.

In 2001, Gordon returned to the H.P. Lovecraft territory with Dagon (2001), and in 2003, directed King of the Ants (2003) about a housepainter-turned-hit man, and brought the David Mamet play Edmond (2005) to the screen.

He contributed to the horror anthology series Masters of Horror (2005) with the episode Dreams in the Witch-House (2005), based on a short story by H.P. Lovecraft. He returned to the series in 2007 with the episode The Black Cat (2007), based on Edgar Allan Poe's story. And in 2008, he directed Eater (2008) for the NBC series Fear Itself (2008).

He is also known for frequently murdering his wife, actress Carolyn Purdy-Gordon, in many of his films.