Houston will be Winfrey's first guest as the television talk-show queen launches her 24th season on Sept. 14. According to her Web site, Oprah.com, Winfrey calls Houston's appearance "the most anticipated music interview of the decade."
The 46-year-old superstar has not done a major TV interview since 2002, when she addressed questions about her drug use from ABC's Diane Sawyer.
Houston is releasing her new album, "I Look to You," on Aug. 31.
She is one of the best-selling artists of all time, but her career stalled as she battled drugs and endured a troubled marriage to Bobby Brown.