The population of the USA was nearly wiped out by a pandemic caused by a deadly fungus 20 years ago. Nature is reclaiming the abandoned cities, and the few survivors are killing each other to obtain food, weapons, and anything else they can get their hands on. The government of the United States collapsed long ago. Most of the uninfected survivors live in quarantine zones controlled by the military, while the infected are left to fend for themselves outside these oppressive safe havens.

After the near-total extinction of the population, nature has taken back the cities. During this time, a struggle for survival begins between two people who must now face it together: the experienced smuggler Joel, who still remembers the world before the pandemic, and 14-year-old teenager Ellie, who grew up in the aftermath of the outbreak. Joel promises a dying friend to take the girl out of the danger zone of Hunter City to another quarantine zone. What seems like a simple job soon turns into a profound journey across the USA.

Factions of hostile survivors, the infected, and a lack of resources make the mission a seemingly insurmountable task for the two who are initially complete strangers. Only together can they overcome the challenges and secure their survival. Bound by their shared fate and significant experiences, a deep and unique friendship develops over time between the mismatched characters. Players will experience the loneliness and dire situation of the two on their journey up close. The story explores themes of loyalty and love, as well as revenge, in a way that has never been seen before in a video game. Players can expect an emotional rollercoaster.