The newspaper reports that Gregory L. Moore announced Tuesday that he will step down April 1.
Moore says he decided to pursue other challenges and that it was time for someone else to lead the newspaper.
During Moore's tenure, the Post won four Pulitzer Prizes and launched a website called The Cannabist, covering the business and culture of legal recreational marijuana. The newspaper also started a news video production unit called DPTV.
Moore came to the newspaper in 2002 from The Boston Globe.
Post Publisher Mac Tully says news director Lee Ann Colacioppo will lead the newsroom during a search for Moore's successor.
The newspaper says Colacioppo is a candidate for the job.