[12] The following year, no longer comfortable in "conservative, God-fearin' Texas",[11] Heard dropped out of her Catholic high school to pursue an acting career in Los Angeles.

[12] Heard's earliest acting work included appearances in two music videos, Kenny Chesney's "There Goes My Life" and Eisley's "I Wasn't Prepared", and small supporting roles in the television series Jack & Bobby (2004), The Mountain (2004), and The O.C.

She made her film debut in a minor role in the sports drama Friday Night Lights (2004), followed by brief supporting roles in films Drop Dead Sexy (2005), North Country (2005), Side FX (2005), Price to Pay (2006), Alpha Dog (2006), and Spin (2007), and a guest-starring spot in an episode of the police procedural crime drama television series Criminal Minds.

[13][14][15] In 2007, Heard played the love interest of the main character in The CW's teen drama Hidden Palms, which the network aired to replace summer reruns of other series aimed at teenage audiences.

That same year, Heard also appeared in the short movie Day 73 with Sarah,[16] in the teen drama Remember the Daze, and in an episode of the Showtime series Californication.

[17] Heard gained mainstream recognition in 2008[18][19] with supporting roles in the Judd Apatow-produced stoner comedy Pineapple Express and the martial arts drama Never Back Down.

[26] In early 2011, Heard also appeared on the British television program Top Gear as a star in a reasonably priced car coming 33rd of 41 on their Cee'd leaderboard.

[30] Heard's third role of 2011 was as the love interest of the main character, played by Johnny Depp, in the Hunter S. Thompson adaptation The Rum Diary (2011).

In 2015, Heard had a prominent role in the comedy-drama Magic Mike XXL, playing the love interest of the film's protagonist, Channing Tatum.

[46] Heard played the female lead in London Fields, an adaptation of Martin Amis's novel about a clairvoyant femme fatale who knows she will be murdered.

[39] Jane Mulkerrins of The Daily Telegraph wrote that Heard provided "a decent enough turn as the enigmatic [Nicola Six]" that still could not save the adaptation,[56] while Peter Sobczynski of RogerEbert.com said that she "just does not project the kind of mystery and allure" that the character requires.

[64] The Chicago Tribune's Michael Phillips and The Independent's Geoffrey Macnab respectively noted that Heard "lends a blasé air of early '50s B-movie cheese" and that she "camps it up entertainingly" as Mera.

[76] Walter Hamada, a former DC Studios president, and James Wan, the film's director, attributed the reduction of Heard's role to the sequel's intention to focus on the relationship between Momoa and Patrick Wilson's characters.

[77][78] Following the release of Aquaman and the Lost Kingdom in 2023, several critics observed that, true to what Heard claimed in court, a number of her scenes seem to have been cut out from the film.

[76] One critic writing for Business Insider stated that "[d]espite WB and Wan's claim, it's tough to believe there wasn't another version of the film where Mera teamed up with her husband to track down his brother and the trio confronted Black Manta.

"[79] Another critic noted that "Heard, a steely highlight of Aquaman, here feels as though her scenes were all added in post" and that "[g]iven the clunky way Mera is literally silenced in the movie... it's hard not to assume that someone important in the production considered her a liability and made a decision of profound, deeply disappointing cowardice: To treat her as radioactive.

[84] Heard traveled to the Mexico–United States border with Amnesty International and worked with the organization on a bilingual campaign to raise awareness about US immigration policies.

[95] In February 2019, Heard joined SAMS' mission to Lebanon to help Syrian refugees living in poverty, during which she visited informal settlements in Beqaa Valley.

[103] In August 2017, Heard produced a short video for the publication, in which she spoke about the gender pay gap and underrepresentation of women in the industry.

[105][106] In August 2016, Heard pledged to donate her $7 million divorce settlement with Johnny Depp to the ACLU and Children's Hospital Los Angeles (CHLA).

[123] Heard wrote an op-ed in The New York Times in November 2019, deeming "revenge porn" an inappropriate label due to the lack of consent for the images' disclosure and emphasizing the importance of congressional legislation to protect privacy in light of state laws' failure.

[123][124] Following her divorce from Johnny Depp,[134] Heard dated tech entrepreneur and Tesla CEO and shareholder Elon Musk for a year, until early 2018.

[152] By December 2015, the case had been adjourned four times with Heard having instructed her lawyers to enter not guilty pleas and stating that she was "looking forward" to fighting the charges.

[153] In the court case in April 2016,[154] Heard pleaded guilty to falsifying quarantine documents, stating that she had made a mistake due to sleep deprivation.

[155] While criminal charges were dropped, she was placed on a A$1,000 (US$752) one-month good behaviour bond for producing a false document;[156] Heard and Depp released a video apologizing for their behavior and urging others to adhere to biosecurity laws.

[156] Heard filed for divorce from Depp in May 2016 and obtained a temporary restraining order against him, releasing a statement saying that, "During the entirety of our relationship, Johnny has been verbally and physically abusive to me.

I endured excessive emotional, verbal and physical abuse from Johnny, which has included angry, hostile, humiliating and threatening assaults to me whenever I questioned his authority or disagreed with him.

[165][166] She dropped her request for a continued restraining order and she and Depp issued a joint statement saying that their "relationship was intensely passionate and at times volatile, but always bound by love.

[169][170] In June 2018,[171] Depp brought a libel lawsuit in the United Kingdom against News Group Newspapers (NGN), the company publishing The Sun, which had labeled him a "wife beater" in an April 2018 article.

[177] In August 2020, Heard filed a counterclaim against Depp, alleging that he had coordinated "a harassment campaign via Twitter and [by] orchestrating online petitions to get her fired from Aquaman and L'Oréal".