The Oscar-nominated Juno filmmaker petitioned an LA Superior Court this week to divorce Lee after more than seven years together, according to legal documents obtained by E! News.
The couple wed in 2004 and are the parents to one daughter, Josie.
Reitman collaborated with Lee, a writer, on the screenplay for Consent, a comic short film about a first date that devolves into a legal dispute.
Lee was a vocal supporter of her husband's films during their marriage, even appearing with Reitman on The Oprah Winfrey Show to promote Up in the Air in 2010.
Young Adult, in which Reitman will direct Charlize Theron and Patrick Wilson, is currently in production.
Reitman has also signed on to helm a film version of Joyce Maynard's novel Labor Day.
> Kate Winslet to star in Labor Day
Watch Jason Reitman and Michele Lee's short film Consent below: