After reading Robert Rodriguez's Rebel Without a Crew (1995) and watching Kevin Smith's Clerks (1994), he began experimenting with his family's video camera.

As associate producer, López took charge of the marketing of Jorge Olguín's horror movie Ángel Negro in 2000, and the adult animation Cesante ("unemployed"), which he co-wrote.

At the age of 20, López directed his first feature film, Promedio Rojo (2004), an absurdist romantic comedy about teenage nerds, in which the main character slips in and out of reality, with the 'unreal' scenes animated.

Although the film was criticized in his native country, it caught the attention of international directors and other industry personalities including Salma Hayek, Alfonso Cuaron, Alejandro González Iñárritu and Guillermo del Toro.

In 2010, after the failure of Santos, López wrote and directed his highest-grossing film yet, Qué pena tu vida, spawning two sequels and building a cast of regular actors such as Ariel Levy, Paz Bascuñán, Lorenza Izzo, Andrea Velasco, Ignacia Allamand, Nicolás Martínez, Ramón Llao and Alison Mandel.

In 2012, López partnered with the American director Eli Roth to release Aftershock, a Chilean-American disaster movie loosely inspired by events that took place during the 2010 Chile earthquake.