"I have had the honor of editing one of the most unique titles in magazine publishing and working with tremendously talented people in our industry," Sischy said in a statement.
"With Sandra Brant's decision to sell her interest in Brant Publications, it is only appropriate that I resign at this time. Sandy and I have worked together as a team, and that has been a huge part of the fun of it. While it is difficult to contemplate being away from this extraordinary experience, the time is right and Interview is firmly positioned for even greater success."
Sischy held the editor-in-chief post at the magazine, which covers art, fashion, entertainment and pop culture, for 18 years.
"When I was first drafted as editor after Andy Warhol's death, I thought I'd stay a few years, devote myself to helping the magazine find its post-Warhol life, and then get back to my writing. Although leaving the magazine and wonderful staff behind is difficult, it is the right decision and one that will allow the new owners to establish their own editorial stamp on the magazine."