Born in Houston, Texas, O'Toole started dancing at the early age of 3. At 13, her family moved to Los Angeles and she began taking acting lessons. Her first big break came when she starred in the 1975 feature film Smile as a conniving beauty pageant contestant. Since then, O'Toole has appeared on the big screen in 48 Hrs. playing Nick Nolte's character's girlfriend, the 1982 remake of Cat People directed by Paul Schrader, Here on Earth with Chris Klein and Leelee Sobieski, One on One, King of the Gypsies, Cross My Heart and Love at Large.

Most recently, O'Toole starred on the cable television series The Huntress and also has been a series regular on Nash Bridges. She has guest-starred on many series including Law & Order, Boy Meets World and Frasier.

She was nominated for Emmy and Golden Globe Awards for her portrayal of Rose Kennedy in the television miniseries The Kennedys of Massachusetts. Her numerous television movie credits include The War Between the Tates as a student involved with her professor; Stand By Your Man, in which she showcased her singing voice playing country music legend Tammy Wynette; Love for Rent, A Girl of the Limberlost, The Entertainer, Stephen King's It and Danielle Steel's Jewels.

Dividing her time between stage and screen, O'Toole has performed in theater productions around the country, including a run in Los Angeles in Vanities and performances of Yankee Wives and Sun Bearing Down at The Globe Theater.