Barton was born in London, England, to an English father and an Irish mother, but moved to New York City when she was four years old. She has two sisters, Hania and Zoe. Barton graduated from the Professional Children's School in Manhattan in 2004.

Barton began her acting career at the age of nine in New York Theatre with a lead role in Slavs!, written by Tony Kushner. She took part in many plays, taking a lead role in James Lapine's Twelve Dreams. She made her film debut in Lawn Dogs, which won awards at film festivals around the world. Since then she has appeared in several films, including The Sixth Sense, Notting Hill, and Lost and Delirious, in which she starred.

Mischa Barton first appeared on television in 1994, as a younger Lily Montgomery in All My Children. She is best known for her current role as Marissa Cooper in the TV series The O.C.. She also had a one-time appearance in the Fox's show Fastlane, and appeared in the video for "Goodbye My Lover" by James Blunt.

Barton is also a model, with such prominent clients as Calvin Klein. She has appeared in advertisements for Aéropostale, Dooney and Bourke, JC (Jeans and Clothes), and Neutrogena. The executives at Neutrogena decided to make her the cover girl for their new worldwide ad campaign; in this regard Barton followed in the footsteps of fellow teen stars Jennifer Love Hewitt, Mandy Moore, and Kristin Kreuk. She also did a commercial for Keds sneakers.

As of the start of Punk'd season six, Barton became the last of The O.C. to get Punk'd.