Mooney was born Debra Vick in Aberdeen, South Dakota, the daughter of Isabel (née Smith) and Henry M. Vick. She was married to stage producer and director Porter Van Zandt until his death in 2012.
From 2012 to 2013, Mooney played the role of Supreme Court Justice Verna Thornton in the second season ofABC drama series Scandal created by Shonda Rhimes. Also in 2014, she had the recurring role in the Netflix comedy series, Arrested Development. In 2014, Mooney joined the cast of The CW series, The Originals in a recurring role as Werewolf Matriarch.