Her first big break came when she worked as a VJ for the television show Total Request Live on MTV. She was supposed to be a guest commentator for one segment, but producers decided to offer her a permanent job. she had a small part on the TV series Dawson's Creek , and this led to her role as Peyton Sawyer on the series One Tree Hill. Burton appeared once on the television series Hey Dude. She made her feature film debut in Our Very Own, a comedy set in 1970s Nashville. Burton was featured on the cover of the Jan/Feb 2004 issue of American Cheerleader magazine. Our Very Own, whose ensemble cast features Allison Janney, Jason Ritter and Cheryl Hines, was screened at the prestigious Sarasota Film Festival, where Burton was honored with a special "Outstanding Ensemble Acting" Award. In addition, the film was nominated for a Independent Spirit Award.

In 2008, she starred in the independent movie The List as Jo Johnston. The film will be released on April 25, 2008. Burton is currently filming a major motion picture called The Secret Life of Bees based on the 2002 novel, Burton will play Deborah Owens. Production began on January 7 2008, in Lumberton, North Carolina.
her newest project is titled The Sacrifice, and it is based on another book by Robert Whitlow (The List). She will be reunited with Malcolm McDowell and Gary Wheeler (director), who are also signed on for the project, which starts filming early next year.

She and husband Ian Prange, an assistant-director for One Tree Hill, reside together in Wilmington, North Carolina, where the show is filmed. She has a cat named after writer Edgar Allan Poe, and is close friends with fellow One Tree Hill stars Bethany Joy Galeotti and Sophia Bush. She has also appeared on the cover of the November 2006 edition of Maxim with One Tree Hill co-stars, Sophia Bush and Danneel Harris. In previous years, Burton has ranked #2 on Femme Fatales: The 50 Sexiest Women of 2005 and named #12 on Much Music's 20 Hottest Women of 2003.