She appears in a Michael Kors black shift dress and pearls in the photo, taken in the famed home's "Blue Room" by White House photographer Joyce N. Boghosian.
Obama is also featured on the March cover of Vogue.
She's the second first lady -- after Hillary Clinton -- to appear on the front of the magazine.
In the interview with Andre Leon Talley, she opens up about helping Sasha, 7, and Malia, 10, adjust to life in Washington, D.C.
"I'm going to try to take them to school every morning -- as much as I can," she says. "But there's also a measure of independence. And obviously there will be times I won't be able to drop them off at all. I like to be a presence in my kids' school. I want to know the teacher; I want to know the other parents."