[citation needed] In 2003, with his brother, Juan de Dios, Larraín co-founded the production company Fábula, through which he develops his cinematic and advertising projects and supports the work of emerging international directors.

[5] In 2012, he released No, in which Gael García Bernal plays an advertising company executive who runs the "No" campaign in the 1988 plebiscite that ultimately voted Augusto Pinochet out of power.

[9] Alongside Tony Manero and Post Mortem, No has been considered a part of an "unintentional trilogy" by Larraín, with all three films being centered around stories set during Augusto Pinochet's dictatorship.

[10] Larraín has said, "In Chile, the right, as part of the Pinochet government, is directly responsible for what happened to culture during those years, not only by destroying it or restricting its spread, but also through its persecution of writers and artists."

He stated that "Chile found itself unable to express itself, artistically, for nearly twenty years" and also felt that "the right wing, throughout the world, is not very interested in culture, and this reveals the ignorance that is probably theirs, because it is difficult for someone to make the most of something or to enjoy it, if you have no knowledge of it".

[12] On 24 March 2014, The Wrap reported that Larraín was in negotiations to direct a new film version of Scarface for Universal Studios, with Paul Attanasio writing the script.

[19] That same year, Larrain made his English-language debut with the Jacqueline Kennedy Onassis biopic Jackie, starring Natalie Portman, Peter Sarsgaard, Greta Gerwig, Richard E. Grant, Billy Crudup, and John Hurt.

[23] In 2020, Larraín participated in the anthology series, Homemade, the series was released on Netflix and consists of several short films following stories during the COVID-19 pandemic, directed by various directors of the world, such as Ladj Ly, Sebastián Lelio, and Rachel Morrison, among others, Larraín directed the short film "Last Call,” starring Chilean actors Jaime Vadell, Mercedes Morán, Delfina Guzmán and Coca Guazzini.

[28] In the 2013 Chilean elections, Larraín supported Michelle Bachelet's center-left presidential candidacy, despite the fact that his parents are members of the conservative right-wing party, the Independent Democratic Union.