In Guerrero, Mexico, Don Miguel braces for competition as he struggles to keep control of the local poppy fields and protect his area. Back in Columbus, Ohio, Detective Mark Edwards orchestrates a traffic stop to close in on a local heroin dealer and starts to work his way up the chain. In Atlanta, Skyler moves back home with his parents to get clean, but a relapse threatens to tear his family apart.

Don Miguel responds to a shooting in his territory as drug-related violence in Mexico continues to escalate. In Columbus, Detective Mark Edwards investigates the overdose death of a young mother and tries to charge the person who gave her the deadly heroin. Nearby in Dayton, Richard runs a recovery clinic while struggling to help his daughter Brittany deal with her own heroin addiction.

In Columbus, Sergeant Nate Smith helps recovering addicts get treatment while zeroing in on a dealer who's mixing heroin with lethal Fentanyl. In Mexico, Don Miguel finds himself trapped in the drug trade, while Mario, a young activist, looks for his missing brother. Back in Atlanta, Skyler signs himself up for long-term treatment but struggles to follow through. Series finale.

In the wake of her husband’s execution by MS-13, Magda fears for her life. She flees Honduras with her young daughter, hoping to make it to the United States. In Colorado, restaurant owner Victor prepares his family for life without him as he awaits his next ICE hearing and possible deportation back to Guatemala. Special Agent Ramirez leads a Homeland Security investigation into a smuggling cell in McAllen, Texas.

With MS-13 hot on their trail, Magda and her brother-in-law Rossni attempt to jump onto the Beast, a cargo train that will take them to the U.S. border. A farming family in Mexico mourns the death of their young son Artemio, who drowned while trying to cross the river illegally into the United States. A female coyota maneuvers to smuggle her migrants across the border in any way possible. Special Agent Ramirez apprehends the leader of a local smuggling cell and attempts to further take down their operation.

At the U.S. Border, Magda and Rossni must split with their group to improve their chances of crossing. Marisa, a human rights activist, helps migrants stuck at the border avoid being trafficked. Sochil, a woman who was sexually abused by leaders of La Luz Del Mundo—a powerful church in Mexico and the U.S.—attempts to expose their sex-trafficking network to Mexican authorities. Homeland Security officers from Texas follow a separate potential sex-trafficking case to Ohio, where they confront a suspect about his relationship with a female minor.

Magda and Rossni cross into the United States, but must now figure out how to manage their asylum case and support themselves. Sochil becomes increasingly worried about her family’s safety and questions whether the Mexican government will ever take action against La Luz del Mundo. A pastor in Honduras attempts to broker a truce between MS-13 and a rival gang at great risk to his personal safety. Juana, a grandmother in Santa Barbara with six kids, faces deportation back to Mexico after living in the U.S. for 20 years. Season finale.

In the border town of Juarez, a trafficker explains how heroin is transported to the US as Mexican Federal police undertake an operation to bust a dealer. In Columbus, Special Agent James executes a significant drug bust and starts tracking the local heroin supply back to its cartel sources when a key suspect disappears. In Atlanta, John hits the street to feed his habit before an impending court date but feels guilty for manipulating his family.

Don Miguel celebrates a birthday as his rivals close in, while Mexican Federal police move to crack down on drug trafficking in Guerrero. In Columbus, Special Agent James tracks down the missing suspect that may be the key to breaking open his case. Meanwhile in Akron, Laura and Dan locate their fugitive son Andrew and convince him to turn himself in for outstanding drug charges and enter rehab.