| Michael Peña | Enrique 'Kiki' Camarena |
| Diego Luna | Miguel Ángel Félix Gallardo |
| Tenoch Huerta | Rafael Caro Quintero |
| Alyssa Diaz | Mika Camarena |
| Joaquín Cosio | Ernesto 'Don Neto' Fonseca Carrillo |
| José María Yazpik | Amado Carrillo Fuentes |
| Matt Letscher | James Kuykendall |
| Ernesto Alterio | Salvador Osuna Nava |
| Alejandro Edda | Joaquín 'El Chapo' Guzmán |
| Fernanda Urrejola | María Elvira |
| Teresa Ruiz | Isabella Bautista |
| Lenny Jacobson | Roger Knapp |
| Aaron Staton | Butch Sears |
| Wagner Moura | Pablo Escobar |
| Alberto Ammann | Pacho Herrera |
| Francisco Denis | Miguel Rodríguez Orejuela |
| Pêpê Rapazote | Chepe Santacruz Londoño |
| Jorge A. Jimenez | Poison |
| Julián Díaz | Blackie |
| Horacio Garcia Rojas | Tomás Morlet |
| Luis Roberto Guzmán | Falcón |
| Vladimir Cruz | Juan Matta Ballesteros |
| Alfonso Dosal | Benjamín Arellano Félix |
| Andrés Almeida | Cochiloco |
| Edmundo Vargas | Cuco |
| Jorge de los Reyes | Antonio Vargas |
| Mike Doyle | Thomas Buehl |
| Natasha Esca | Suzy |
| Julia Lehman | Rita Knapp |
| Jessica Lindsey | Ronnie Sears |
| Tania Arredondo | Ana Kuykendall |
| J. Downing | Bud Mullen |
| Guillermo Villegas | Sammy Álvarez |
| Antonio Fortier | DFS Officer |
| Michelle Ampudia Vieth | Clara Knapp |
| Ian Laiter Steiglitz | Billy Knapp |
| Sergio Gutierrez | Laborer |
| Alessandro Borrelli | Kiki Jr. |
| Jonathan Ochoa | Miguel Jr. |
| Ivana Plantier | Abril |
| Mark Kubr | Tony |
| Claudio Roca | |
| Scoot McNairy | Narrator |