The director, who was behind the original film in 1984 and its subsequent sequel in 1989, has decided to hand over the responsibility to a new filmmaker.
The studio has begun a search for that director, said the Hollywood Reporter.
It is the latest setback for the third film following the death of original cast-member Harold Ramis recently.
Ramis co-wrote and starred in the first two films along with Dan Aykroyd and Bill Murray and was set to make a cameo in the third film.
Reitman, however, will keep his association with the project as a producer.
Sony is eyeing a start early next year.