She made her film debut in 2004 in the sports drama Friday Night Lights, starring Billy Bob Thornton.

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Heard is involved in social activism for causes such as LGBT rights and is a supporter of Habitat for Humanity; Girl Up, a United Nations Foundation campaign; The Art of Elysium; and Amnesty International.

While in Los Angeles, Heard made appearances in several TV shows and two music videos, Kenny Chesney's "There Goes My Life" and Eisley's "I Wasn't Prepared". Her first movie role was Maria in Friday Night Lights (2004), starring Billy Bob Thornton.

She was cast as Liz in the pilot episode of The WB's Jack & Bobby (2004), as Riley in an episode of The Mountain (2004) and she had a guest starring role as a salesgirl in The O. Based on actual events, the movie was both a commercial and critical success.

She next starred as Shay in Side FX (2005), an independent horror film, and had supporting roles in Drop Dead Sexy (2005), Price to Pay (2006) and You Are Here (2006).

Heard had a more prominent role in Niki Caro's North Country (2005), in which she played the teenage version of Josey, Charlize Theron's character. On the show she portrayed Greta Matthews, who suffered the losses of both her mother and boyfriend, Eddie, and befriends Johnny, the antihero of the show.

In order to get the part, Heard was asked to lose weight.It took her four months between the pilot and the second episode to lose 25 pounds, giving up alcohol, increasing her workouts and following a macrobiotic diet (no meat, dairy or processed sugar).Her appearance in films such as The Informers, The Stepfather, Zombieland and The Joneses brought her further attention.She next starred in John Carpenter's The Ward, alongside Nicolas Cage in Drive Angry, and alongside Johnny Depp in The Rum Diary, for which she won a Spotlight Award at the Hollywood Film Festival.In 2014 she appeared in 3 Days to Kill, and in 2015 in Magic Mike XXL and The Danish Girl.In 2017, Heard will appear as Mera in Zack Snyder's upcoming superhero film, Justice League.