She attended John Burroughs School in St. Louis, Missouri (along with Mad Men star Jon Hamm, who was her prom date), and Indiana University, where she studied Fine Arts and Italian. During that time she also dated fellow actor Paul Rudd for a short time. While a student at IU, Clarke became a member of the Kappa Alpha Theta sorority. She was initiated into the Beta chapter in 1990.
Clarke began her acting career with an appearance in a 1999 award-winning commercial for Volkswagen. She followed this with a role in the 2000 short film Pas de deux and received an Outstanding Performance award at the Brooklyn Film Festival. Clarke's career soon blossomed with minor roles, including films All About George in 2000 and The Accident in 2001, as well as television shows such as Ed and Sex and the City.
In 2001, Clarke auditioned for the role of CTU agent Nina Myers on 24. She won the role on the day that filming began. The wardrobe department didn't have time to fit her, so she had to wear her own outfit for the entire season of filming. In her three seasons with the show, Clarke was featured in a total of 36 episodes. Clarke won a Golden Satellite Award for Best Performance by an Actress in a Supporting Role in a Drama Series for this role. Clarke also lent her voice to 24: The Game, as her 24 character, Nina Myers.
Clarke met her husband, Xander Berkeley, while on the set of 24 (he played her supervisor, George Mason) and they were married in September 2002, a year after meeting. They have two daughters: Olwyn Harper (born on September 23, 2006) and Rowan (born c. March 2010).
She has guest-starred on House and Life. She played Renée Dwyer, Bella Swan's mother, in Twilight. She accepted a leading role on new TNT series entitled Trust Me, opposite Eric McCormack and Thomas Cavanagh. The series premiered on January 26, 2009 to positive reviews, though it was cancelled after one season due to declining ratings. In 2010, Clarke reprised her role as Renée Dwyer in Eclipse, the third movie in the Twilight series. In 2013, she was cast as Marla Jameson in the US version of The Tomorrow People.
