Peli began as a computer software programmer, being one of the developers behind Photon Paint, a bitmap graphics program for the Amiga. His first film Paranormal Activity was inspired by Peli moving into his first house alone and without family nearby. Peli would hear creaks and knocks in the night, which laid the groundwork for a film about a family running around with cameras trying to catch what was going on in the house.
After the success of Paranormal Activity, Peli worked with James Wan and Leigh Whannell to develop Insidious. Peli also produced and wrote the 2012 horror film, Chernobyl Diaries, based on the Chernobyl disaster and on his story The Diary of Lawson Oxford. The film followed "a group of friends who, while vacationing in Europe, find themselves stranded in the abandoned city of Prypiat, Ukraine only to discover that they are not alone."
In 2012, The River premiered on ABC, a paranormal/action/horror television series about a group of people on a mission to find a missing TV explorer in the Amazon. Oren Peli co-created the show with Michael R. Perry who co-wrote Paranormal Activity 2.
Peli is working on The Lords of Salem and Area 51. He is the screenwriter and director of Area 51, a story about three friends who want to discover the secrets of the fabled Area 51. The Lords of Salem, written and directed by Rob Zombie, is set in the town of Salem, MA as it is terrorized by a coven of witches. Oren Peli is also producing Paranormal Activity 5, the sixth installment in the Paranormal Activity franchise.