Two decades after a cordyceps-type fungus has infected millions, systematically taking over their brains and turning them into The Infected, nature has gradually retaken the abandoned cities and towns. Survivors are hemmed inside quarantine zones, completely under the heel of the United States military, with order and screening for any infected being viciously maintained under martial law.
Joel, a smuggler within a quarantine zone in Boston, sells weapons and drugs on the black market for ration cards that he can trade for goods, supplies, or favors. When a shipment is stolen, Joel and his partner Tess head to track down the thief and find themselves smuggling their most difficult cargo ever, a young girl named Ellie. Charged with smuggling Ellie out of the quarantine zone and into the hands of the Fireflies, an organization that fights military oppression, the three must survive the scavengers, hunters, and the infected when the plan goes to hell and their escort is killed.