Talley was born in the community of Hayti, Durham, North Carolina, as the son of Alma Ruth Davis and William C. Talley. His parents left him with his grandmother, Bennie Davis, who raised him and, he claims, gave him an „understanding of luxury.“ After graduating from North Carolina Central University, Talley received his master’s degree in French from Brown University. While at Brown, Talley befriended students from the nearby Rhode Island School of Design and often went on weekend trips to New York City. He is associated with former American Vogue editor-in-chief and Costume Institute consultant, Diana Vreeland. His first job was as an assistant for Andy Warhol for $50 a week.
In the mid-2000s, an intervention was initiated by Anna Wintour, to get Talley to lose weight. As seen on The Oprah Winfrey Show, he eventually lost a great deal of weight, and was eating more healthily.
In 2008, Talley advised the future First Family on fashion, and introduced Michelle Obama to the Taiwanese Canadian designer Jason Wu, from whom she bought several dresses including her inaugural gown.
He had a cameo appearance in the 2008 movie Sex and the City as a Vogue executive. He also appears in the movie-documentary about the Italian couturier Valentino Garavani,Valentino: The Last Emperor and in the documentary The September Issue. In October 2011, the André Leon Talley Gallery opened in the new Savannah College of Art and Design Museum of Art. He also made a cameo in Mariah Carey’s „Say something“ video.