Born and raised in New Orleans, Clarkson studied drama at Yale. Her feature-film debut was in The Untouchables (1987) as the wife of Elliot Ness.
She garnered attention for her role as the drug-addicted Greta in the independent film High Art.
In television, she had reoccuring roles on Wonderland and Frasier, and won an Emmy for her role in Six Feet Under.
Other film roles include The Green Mile, the Russo brothers' Welcome to Collinwood, Todd Haynes' Far From Heaven, and Lars von Trier's Dogville.
In 2003, Clarkson won the Outstanding Performance award for her work in All the Real Girls, The Station Agent, and Pieces of April.