Barton later appeared in the independent drama Lost and Delirious (2001) and guest-starred as Evan Rachel Wood's girlfriend on ABC's Once and Again (2001–02). She played Marissa Cooper in the Fox television series The O.C.(2003–2006), for which she received two Teen Choice Awards. The role brought Barton into mainstream fame, and Entertainment Weekly named her the "It Girl" of 2003.
Barton has since appeared in the comedy remake St Trinian's (2007), the Richard Attenborough–directed drama Closing the Ring (2007) and Assassination of a High School President (2008). She returned to television, starring in the short-lived Ashton Kutcher-produced CW series The Beautiful Life (2009).
In 2012, she returned to the stage, performing in the Irish production of Steel Magnolias. She also appeared alongside Martin Sheen in Bhopal: A Prayer for Rain (2014). She has garnered critical praise for her roles in independent films, with the Los Angeles Times praising her "standout" performance in Starcrossed (2014). Barton was cast in the first season of the MTV series The Hills: New Beginnings (2019–2021), a reboot of The Hills. In 2023, she was cast in an extended guest role for the rebooted Australian soap opera Neighbours on Amazon Freevee and Network 10.
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