Buttgereit has been experimenting with film since 1977. His first project was called Gags und Schwarzer Humor, a parody of TV commercials. Color Trip was created after his camera broke and the developers gave him back black, blank film. After scratching and washing the film, something blue, black and green came out of the projector. Klassenfahrt was a movie about his class in his last year at school. Stress was another version of Color Trip using another returned blank film. He claims his very first feature was called Interview with Frankenstein.

The Exploding Sports Shoe (1980) was a two-minute film consisting of a Sports shoe exploding in slow-motion. It was shown on TV as part of a documentary about punk rock, the original title was 'The Most Beautiful Destruction'.

He is best known for his 1987 film Nekromantik.

In 1999, he directed an episode of the television series Lexx, after a six-year absence from the entertainment industry.

In 2012, speaking at the Leeds International Film Festival, Buttgereit said that he was happy working in stage and television production and cited internet piracy as a Problem for low-budget filmmakers.

Buttgereit's superhero character, Captain Berlin, was adapted into a comic book series in 2013. There is currently a comic book version of Nekromantik being made.

In 2013, Buttgereit announced that he would be teaming up with fellow horror Directors Andreas Marschall and Michal Kosakowski to work on an anthology film called German Angst, in which each Director would do one short. The film was released on May 7 2015.