Moira was raised in Ronkonkoma, NY. She attended Connetquot Senior High School and graduated in the class of 1986. Later Moira attended Marymount Manhattan College. In 1984 Moira was cast in a small role in Connetquot Senior High School's production of Annie. Due to illness, the young woman playing Miss Hannigan was replaced, causing a series of cast changes. Director Eric Martinsen chose to recast Moira as Grace Farrell. She was a great success, and so began her career.
She has appeared in the movies With Honours, Little Odessa, The Tie That Binds and Dangerous Beauty amongst others, and provided the adult voice of Nala in Disney's The Lion King, The Lion King II: Simba's Pride, and The Lion King 1½. In her independent film career, Kelly had the starring role of activist Dorothy Day in Entertaining Angels: The Dorothy Day Story and starred alongside Glenn Close in The Safety of Objects. She played Helen Keller in the made-for-TV movie Monday After the Miracle, which broadcast on November 15, 1998, on CBS.
Kelly starred in the CBS drama To Have & to Hold opposite Jason Beghe before playing Mandy Hampton in the first season of The West Wing. In 2003, Kelly began playing single mother Karen Roe on the teen drama One Tree Hill. She also directed two episodes of the series: "Resolve" (2007) and "I Slept with Someone in Fall Out Boy and All I Got Was This Stupid Song Written About Me". She has made guest appearances on television shows such as Heroes, Law & Order, and Numb3rs. Kelly has also appeared in the films Remember the Daze, A Smile as Big as the Moon and Taken Back: Finding Haley.