2003. As a parasitic fungal outbreak begins to ravage the country and the world, Joel Miller attempts to escape the escalating chaos with his daughter and brother. Twenty years later, a now hardened Joel and his partner Tess fight to survive under a totalitarian regime, while the insurgent Fireflies harbor a teenage girl with a unique gift.

After a harrowing trek across a desolate United States, Joel and Ellie find themselves navigating a dangerous Kansas City on foot. Later, rebel leader Kathleen instigates a manhunt – one that pits her violent civilian militia against the world's best hope.