Born and raised in New Orleans, Clarkson made her acting debut in high school plays. Afterwards, Clarkson attended Louisiana State University where she studied speech for two years, but she couldn’t ignore her love of performing and switched to Fordham University in New York, where she graduated summa cum laude with a degree in theater arts. She then went on to earn her M.F.A. at the Yale School of Drama.
Clarkson made her professional acting debut in New York, where she appeared in a number of stage productions both on and off Broadway. She received Outer Critics Circle and Drama Desk nominations for her role in the play Maiden’s Prayer. Her television debut came in 1995 in the TV series Spenser: For Hire, followed by a guest appearance on The Equalizer in 1996. Shortly after, she made her feature debut playing the role of Catherine Ness in The Untouchables (1987), opposite Kevin Costner. Roles in features such as The Dead Pool (1988) and Rocket Gilbraltor (1988) quickly followed, and the husky-voiced actress found herself in demand. In 1991, she landed a regular role in the TV series Davis Rules, then played roles in a number of TV movies over the next few years, including An American Story (1992), Legacy of Lies (1992), Blind Man’s Bluff (1992), Caught in the Act (1993) and She Led Two Lives (1994). In 1995 Clarkson returned to features with Jumanji(1995), but later that year was back on television with a regular role in Murder One. After a year on the series, she found herself once again doing features, winning a Saturn Award for her role in The Green Mile (1999), starring Tom Hanks.
The awards began pouring in during 2002, when Clarkson won an Emmy for “Outstanding Guest Actress in a Drama Series” for the TV series Six Feet Under, a “Best Female Performance” award from the Deauville Film Festival for her role in The Safety of Objects (2001) and a New York Film Critics Circle “Best Supporting Actress” award for her supporting role in the feature film Far From Heaven (2002). The awards kept piling up the following year when she won a National Society of Film Critics Award for her role in Far From Heaven (2002) and a Special Jury Prize at the Sundance Film Festival for her role in The Station Agent (2003). In 2004, she received her highest actor honor to date—an Academy Award nomination for her role as a dying mother in Pieces of April (2003). In 2006, she received her second Emmy as “Outstanding Guest Actress in a Drama Series” for the TV series Six Feet Under. In 2009 she received the Independent Award for Excellence in Acting at the ShoWest Convention.