He is known for his performances in the films Amores perros (2000), Y tu mamá también (2001), Bad Education (2004), The Motorcycle Diaries (2004), Babel (2006), Coco (2017), Old (2021), and Cassandro (2023).

He has also played music conductor Rodrigo de Souza in the television drama series Mozart in the Jungle (2014–2018), and has starred in the Disney+ special Werewolf by Night (2022).

[8][9] He began studying philosophy at UNAM, Mexico's national university but, during a prolonged student strike, he decided to take a sabbatical to travel around Europe.

[citation needed] His next role was Alfonso Cuarón's Y tu mamá también (2001), which was a crossover success into American markets and gained him notice on the international stage, becoming the second-highest grossing Spanish language film in the United States.

The film broke the box office record set 3 years prior by Y tu mamá también, and garnered Bernal a BAFTA nomination in 2005 for Best Performance by an Actor.

[citation needed] García Bernal has worked for acclaimed directors including González Iñárritu, Pedro Almodóvar, Walter Salles, Alfonso Cuarón, Michel Gondry, and Iciar Bollaín, among others.

The company recently joined with Golden Phoenix Productions to produce a number of television documentaries about the unsolved murders of more than 300 women in the border city of Ciudad Juarez.

[20] For the third time García Bernal appeared with Diego Luna in the American Spanish-language comedy film Casa de mi padre, opposite Will Ferrell, where he played a feared drug lord.

[21] García Bernal's next projects included a film adaptation of José Agustín's Ciudades Desiertas and the Jon Stewart directorial biopic Rosewater,[22] in which he portrayed Maziar Bahari to widespread critical acclaim.

[citation needed] In 2014, he was cast in the lead role of Rodrigo de Souza in the Amazon Studios comedy-drama television series Mozart in the Jungle.

[citation needed] In 2016, he starred in two movies that were submitted for the Academy Award for Best Foreign Language Film, Desierto (Mexico) and Neruda (Chile).

[27] In October 2019, García Bernal and Diego Luna announced they were joining the Creative Advisory Board for TV and Film development company EXILE Content along with Adam Grant.

[30] In 2024, he starred alongside close friend and frequent collaborator Diego Luna in the Hulu Original miniseries, La Máquina as the eponymous character.