A pregnant woman runs through the woods, groaning as labor pains hit. Infected scream in the distance. And Anna keeps going, running for the safety of a house. She calls out for help but nobody’s home. Anna locks the door behind her as the infected get closer. As she climbs the stairs, her waters break.
Anna hides in a room and barricades the door, grunting as another contraction hits. Glass breaks and she pulls out a familiar switchblade. A runner smashes the door until it opens, lunging for Anna.
Their struggle ends with her stabbing it in the head. A stunned Anna looks down to see two things: her newborn baby daughter on the floor, and a bite on her own thigh. It’s already thick with fungus. Desperate to save her baby from infection, Anna cuts the chord. She holds the baby close and calls her Ellie.
After dark Marlene and two others come back to the house. Marlene follows the sound of Anna singing, finds her cradling the baby and singing. Anna has a knife at her own throat, ready to kill herself before she turns.
Marlene’s full of apologies, but Anna knows she’s running out of time. She tells Marlene the baby’s hungry because Anna hasn’t fed her, not wanting to infect her daughter. Then Anna lies, promising Marlene she cut the chord before she was bit. Invoking their lifelong friendship, Anna gives Marlene instructions to pick up Ellie then kill her. Though she’s reluctant, Marlene obeys. She and baby Ellie both cry after the gunshot.
Present day Ellie is zoned out, sat on an abandoned truck. She doesn’t hear Joel calling. He’s found more of her favorite food and a game. They leave the highway to search for a local hospital, which Joel thinks is St Mary’s – the Firefly base. He talks about teaching Ellie guitar in the future, concerned by how dazed she is.
Ellie guesses his plan to cut through a building and find a skyscraper to see across the city. And this time it’s Joel who cracks jokes, trying so hard to make Ellie smile. They go through a construction site, Joel boosting Ellie up to pass him a ladder. But she drops it, running off. Joel curses and follows as fast as he can. But Ellie sprints on, calling for him to hurry up, more excited than she’s been about anything since David took her prisoner.
Together they take in the magic of a giraffe. Joel hands Ellie more leaves to feed it. And Ellie laughs. Joel looks at her with the same wonder she has for the giraffe. Finished eating, the giraffe moves on. And an ecstatic Ellie races through the building so they can watch it go.
Joel worries about the journey ahead, telling Ellie they don’t have to go to the Fireflies to make the vaccine. He suggests going back to the comfort of Jackson. But Ellie insists they go to the hospital because everything she’s done, and the people they’ve lost, can’t be for nothing. Ellie promises to go wherever Joel wants after making the cure; that she’ll follow him anywhere.
They cut through an abandoned emergency medical center left over from the outbreak. Joel talks openly about his past, admitting that he ended up in a similar place after being shot on day two. After Sarah died, Joel tried to end his own life because he couldn’t see the point in going on without her. Ellie says that time heals all wounds. And Joel looks at her, says “It wasn’t time that did it.”
Joel asks Ellie to read more jokes from her book. Behind them men in army gear sneak up and throw a smoke grenade. Joel shields Ellie with his body. They lie in the smoke, dazed and confused. A soldier snatches Ellie while she screams for Joel. The other knocks him out with a rifle.
Joel wakes in a hospital. And Marlene welcomes him to the Firefly base. Immediately he asks about Ellie. And Marlene’s amazed they made it when she lost half her team crossing the country. Outside the hospital room, armed Fireflies stand guard. All Joel wants is to go to Ellie – but Marlene refuses.
Ellie’s being prepared for surgery. As Joel asks question after question, Marlene explains that the cordyceps has grown with Ellie since birth. It creates a chemical that tricks the other cordyceps into thinking they’re the same. Marlene shares the plan to remove this miracle strain from Ellie, multiply it in a lab, and make a vaccine that saves humanity.
Joel has a terrible realization: cordyceps grows in the brain. Ellie’s life is the price of saving the world. He begs Marlene to find someone else. But Ellie’s one of a kind. A soldier restrains Joel as Marlene admits they kept the truth from Ellie so she wouldn’t get scared.
The Firefly knocks Joel to the ground as he struggles, begging for Ellie’s life. Marlene says she understands his pain, having loved Ellie since she was born. She instructs her soldiers to walk Joel to the highway and pass on Ellie’s switchblade, giving permission to kill Joel if he resists.
Two Fireflies lead Joel through the hospital. Halfway down the stairs Joel stops walking. When a soldier comes at him, Joel takes his gun, executing both Fireflies. He takes their machine gun and ammo.
Drawn by gunfire, the Fireflies track Joel. And he prowls through the corridors, shooting them without hesitation. Even when a Firefly surrenders, dropping his weapon, Joel has no mercy. When Joel runs out of bullets he uses Ellie’s switchblade, stabbing a Firefly who begs for his life and taking a fresh gun.
Joel blasts his way to the top floor, leaving a trail of bodies in his wake. He finds the surgical team in gowns and gloves, standing over a sleeping Ellie. Joel demands they unhook her from the machines.
The lead surgeon picks up a scalpel, saying he won’t let Joel take Ellie. And Joel shoots him in the head while the others scream.
The nurses do as Joel asks, taping up Ellie’s wound and turning around. He lifts an unconscious Ellie from the table, walking past the dead surgeon, and gets in the elevator. The enormity of his actions hits Joel on the way down. But he doesn’t stop, carrying Ellie to a parked car.
Marlene’s armed and waiting. She tells Joel he can’t keep Ellie safe forever, pointing out that a violent death is almost inevitable in a broken world – which Ellie’s sacrifice could save. They both know Ellie would give up her life to make a cure. Joel gets emotional, and Marlene lowers his gun, assuring him they can still fix things. Joel looks at Ellie asleep in his arms.
Then Joel’s driving along an open road. Ellie wakes up confused in the back seat. Joel lies to her, claiming there were other immune people but a cure wasn’t possible. A flashback shows him shooting Marlene in the gut.
Shocked, Ellie asks where her clothes are. Joel claims raiders attacked the hospital and they barely made it out alive, promising to get her new clothes on the way to Jackson. Ellie asks if people were hurt, wanting to know about Marlene. Joel has no answer. And Ellie rolls over, unable to look at him.
Joel apologizes. And a flashback shows him loading Ellie into the backseat while Marlene – still alive – groans. She begs Joel to let her go. “You’d just come after her,” he says, and puts a bullet in Marlene’s skull.
They drive through the night to Wyoming, until the car gives out. Ellie traces the fungus in her arm. On the walk back to Jackson Joel opens up about hiking with Sarah, and his certainty she and Ellie would have liked each other though they’re very different.
On the hill overlooking Jackson Ellie reveals she and Riley were bit together, admitting to killing Riley after she turned. Ellie lists the people who have died, and Joel tries to convince her she’s not to blame. Ellie interrupts, making Joel swear what he said about the Fireflies is true. He looks her in the eye and promises. Though Ellie looks uncertain, she nods.
