Eli Raphael Roth was born in Newton, Massachusetts, to Cora (Bialis),a painter, and Sheldon H. Roth, a psychoanalyst, psychiatrist, and clinical professor. His family is Jewish, with roots in Austria, Hungary, Russia, and Poland.
Roth began making Super 8 films at the age of eight, inspired by Ridley Scott's Alien. He made over 50 short films with his brothers and friends before attending New York University's Tisch School of the Arts, where he won a student Academy Award and graduated summa cum laude in 1994.
After film school, Roth worked in film and theater production in New York City, taking on various roles from production assistant to assistant editor to assistant director. At 20, he became development head for producer Fred Zollo, but soon left to focus on writing full-time.
Roth co-wrote the script for Cabin Fever with friend Randy Pearlstein in 1995, but the film took years to get financed. In 1999, he moved to Los Angeles and within four months secured funding for his animation series Chowdaheads.
Roth went on to produce, direct, and design The Rotten Fruit, a stop-motion series, and worked with David Lynch on content for his website. In 2001, he filmed Cabin Fever on a shoestring budget of $1.5 million, which became a critical and commercial success, grossing over $30 million worldwide.
Roth used the success of Cabin Fever to launch a slew of projects, including The Box, a horror thriller co-written with Richard Kelly. In 2003, he co-founded Raw Nerve, LLC, a horror film production company with Boaz Yakin, Scott Spiegel, and Greenestreet Films.
In 2014, Roth married Chilean model and actress Lorenza Izzo.