He has frequently collaborated with filmmaker Wes Anderson, appearing in his films The Darjeeling Limited (2007), Fantastic Mr. Fox (2009), The Grand Budapest Hotel (2014), The French Dispatch (2021), and Asteroid City (2023).

[15] Taking acting classes as a child, by age thirteen, Brody appeared in an Off-Broadway play and a PBS television film.

[17] Director Roman Polanski had seen Brody's performance in Harrison's Flowers (2000), and decided to offer him the leading role in The Pianist (2002).

[18] To prepare for the role, Brody withdrew for months, gave up his apartment and his car, and took piano lessons for four hours a day until he could master passages from some of Chopin's finest works.

In Dummy (released in 2003, but originally shot in 2000, just prior to his work in The Pianist), he portrayed Steven Schoichet, a socially awkward aspiring ventriloquist in pursuit of a love interest (his employment counsellor, played by Vera Farmiga).

He learned ventriloquism and puppetry for the role (under the tutelage of actor/ventriloquist Alan Semok) convincingly enough to perform all of the voice stunts and puppet manipulation live on set in real time, with no subsequent post dubbing.

He played Noah Percy, a mentally disabled young man, in the film The Village, by M. Night Shyamalan, shell-shocked war veteran Jack Starks in The Jacket, writer Jack Driscoll in the 2005 King Kong remake, and father-to-be Peter Whitman in The Darjeeling Limited by Wes Anderson.

King Kong was both a critical and box office success—it grossed $550 million worldwide, and is Brody's most successful film to date, financially.

[20] On January 5, 2006, Brody confirmed speculation that he was interested in playing the role of The Joker in 2008's The Dark Knight, and also met with director Christopher Nolan.

[36] The Leopard Club Award pays homage to a major film personality whose work has made a lasting impact on the collective imagination.

[38] In 2024, Brody starred in Brady Corbet's The Brutalist, replacing Joel Edgerton in the lead role and joining an ensemble cast consisting of Felicity Jones, Guy Pearce, Joe Alwyn, Jonathan Hyde, Emma Laird, and Peter Polycarpou.

[51] In February 2020, it was reported that he was in a relationship with English fashion designer and actress Georgina Chapman, whom he began dating while she was still married to but in a formal separation from Harvey Weinstein.

[52] At the 75th Academy Awards in 2003, Brody became the subject of controversy while receiving his Best Actor Oscar for The Pianist, when he passionately kissed the presenter, actress Halle Berry.

[59][60][61][62][63][c] After being widely viewed as the 2003 Oscars' signature moment,[53][65][63][67][68] Brody's behavior inspired a number of televised parodies that year.

[54] In January 2025, Halle Berry congratulated Adrien on his Instagram profile, for winning the Golden Globe Award for Best Actor for his performance in The Brutalist.