March was born to John Abe March IV and Laura Len Irwin in Dallas, Texas. She attended Highland Park High School, the same high school Angie Harmon (of the original Law & Order) attended. March was a sophomore when Harmon was a senior. She began performing in plays in high school. In 1996 she graduated from the School of Speech (now School of Communication) at Northwestern University, where she majored in Theater and Hispanic Studies. After graduating, she landed her first professional acting role (in her very first audition) as Helena in A Midsummer Night's Dream in Chicago, where she continued to pursue her stage career.

In 1999, March made her Broadway debut in the highly acclaimed production of Arthur Miller's Death of a Salesman, opposite Brian Dennehy. Her other career highlights include roles on the television series Early Edition and in the TV movie Since You’ve Been Gone.

Her biggest career success to date has been her role as Alexandra Cabot on the NBC crime drama Law & Order: Special Victims Unit, a role she played from 2000 to 2003. She has also appeared in the Chris Rock comedy Head of State and the Brad Pitt/Angelina Jolie vehicle Mr. & Mrs. Smith. March reprised her role as Alexandra Cabot, now a Bureau Chief, on the short-lived NBC courtroom drama Conviction, which debuted in spring 2006.

March posed for Maxim Magazine in 2000 and also performed in the Broadway debut of Eric Bogosian's Talk Radio, starring Liev Schreiber Performances began February 15, 2007 at the Longacre Theater.

March lives in New York City. She loves to travel and enjoys swimming, yoga, and dance in her free time. She married chef Bobby Flay on February 20, 2005; he proposed to her while ice skating at Rockefeller Center on December 19, 2003.