He is most well known for directing the controversial Mexican crime thriller Heli for which he was awarded the best director prize award at the 2013 Cannes Film Festival, and for directing the 2016 Mexican drama The Untamed for which he received the Silver Lion for best director at the 2016 Venice Film Festival.

[3] Escalante was incidentally born in Barcelona, Spain while his parents — a Mexican father and an American mother[4] — had been living in Norway.

[5][6] He spent most of his early years in Guanajuato, Mexico,[2] but moved to Spain in 2001 to study film editing and sound at the Center for Cinematographic Studies of Catalonia (Centre d'Estudis Cinematogràfics de Catalunya, CECC)[7] and apply for Spanish citizenship; which he failed to secure.

[5] After his stint in Barcelona, he joined the International School of Film and Television (EICTV) in Havana, Cuba[7] an institution founded by Nobel Prize-winner Gabriel García Márquez, Fernando Birri and the Julio García Espinosa "to support the development of national audio-visual industries" in non-aligned countries.

He worked as an assistant of Carlos Reygadas in Batalla en el cielo (2005), which entered the 2005 Cannes Film Festival.