At the beginning of the movie, Jonah, three of his men, and his girlfriend Lydia break into a house where they kill one of the inhabitants. Jonah orders the horrified Lydia to shoot the man's wife but Lydia panicks and accidentally shoots Jonah in the neck instead, seemingly killing him. Lydia flees from the wrath of Jonah's henchmen to her father John but is pursued by Jonah's gang. Lydia and John flee but are followed not only by Jonah's henchmen but also by a Sicario, a "cleaner" for a mexican drug cartell.
After barely escaping the Sicario multiple times, John visits his old friend Arturo in prison and finds out that Jonah is the nephew of a Mexican crime lord but betrayed him. To prevent his uncle from finding out, which would result in a horrible death for Jonah, Jonah was covering his tracks by killing his own men. Arturo, who wields influence over a gang in the prison, promises that if any of Jonah's men would be imprisoned, he would take care of them.
While John is in prison, Lyida is called by John's friend Kirby. Kirby tells her that she should visit a crowded place in order to be safe. When Lydia, who follows Kirbys advice, heads to a cinema in town she is called by an unknown number. Lydia expects her father to be calling but it is Jonah. Jonah claims that with help from "underground doctors" he managed to survive but is in constant pain and will never be the same. He also seems aware that Lydia is in a cinema. Lydia expects that he is merely tracking her number but Jonah reveals himself to be present and standing right next to her. Lydia is kidnapped by Jonah's men and they drive into the desert with her.
In the desert, Jonah calls John from Kirby's phone. He orders Kirby, who lies tied up in the trunk, to speak to John and then shoots him in the torso multiple times, killing him. By revealing what he knows about Jonah's operation and claiming that the Sicario his uncle sent Jonah does not only serve Jonah, but keeps an eye on him as well and would kill him instantly should his uncle order it, John convinces Jonah to meet him in the desert.
In the desert, John surrenders himself to Jonahs men and is captured. Jonah's men pull him in their car and Jonah orders them to drive to another location in case John has been followed. John however had rigged the motorbike he arrived with with explosives and when it blows up, John uses the distraction to kill Jonah's men. Jonah escapes the car and flees into the desert while the Sicario is covering him from a nearby hill. Although John and Lydia manage to kill the Sicario, John is mortally wounded and dies in the arms of his daughter.
Although Jonah was able to escape the ambush, he is caught by the police while trying to escape through the desert. He is imprisoned and is last seen cornered on a table by multiple prisoners, including Arturo who smiles knowingly, implying that he will be killed.