Ann Burden is a teenage girl who thought she was the last survivor of a nuclear war. Since her family's disappearance on a search expedition, she has lived alone on her farm in a small valley spared from radiation poisoning. In late May, a year after the war, a stranger in a radiation-proof suit approaches her valley. Afraid he might be dangerous, Ann hides in a cave. Watching from a distance, Ann does not warn the man when he mistakenly bathes in a radioactive stream. But when he sickens, her fear of being alone forever leads her to reveal herself to help him.
The stranger is John Loomis, a chemist who helped design a prototype radiation-proof “safe-suit” at an underground lab near Ithaca, New York. After searching many months for survivors, he found Burden Valley. Ann is impressed by Loomis's calm explanation of his (possibly fatal) radiation sickness, thinking she would be hysterical in his place. Loomis is amazed the valley is radiation-free (a "meteorological enclave"). After Ann moves him into her house, he explains how to get gas manually for the tractor and begins planning a hydroelectric generator. Having the companion she often wished for, Ann imagines eventually marrying him, but decides not to discuss it until he recovers. Still, she thinks wistfully of having children someday. While plowing, she remembers lines from a favorite poem, Millay's "Epitaph for the Race of Man," happy that she is no longer the scribe and confessor of Earth like the speaker in the poem. But she wishes she had warned Loomis about the stream.
As Loomis becomes more ill and delirious, he has traumatic flashbacks to the underground lab, and talks of how he shot his coworker, Edward, who tried to take the safe-suit to find his family. Deeply troubled that Loomis killed a man, Ann debates whether he is a murderer. She thinks that he might have acted in self-defense, for if Edward had taken the suit and not returned Loomis would have eventually died in the lab. He might also have intended to use it to find other survivors. But Ann also worries that Loomis might have killed Edward to keep the suit for himself, so he could leave the lab and "strike out on his own." Still, Ann prays Loomis will live even though he could be a murderer. She nurses him through his illness and keeps secret her knowledge of Edward's death. The first time he speaks again, saying her companionship saved him, she restrains an urge to hug him and sits by his bed, listening. As Loomis slowly recovers, Ann is taken aback when he begins criticizing her use of time and resources and to give her orders. He scolds her for not yet planting corn, in what she thinks is the same voice he used to speak to Edward in his delirium. He forbids her to touch the safesuit after she suggests she could use it to get books.  He orders her to plant wheat and beets to preserve seed stock, and though she acknowledges this is sensible, his explanation that they have to plan "as if this valley is the whole world and we are starting a colony," makes her uneasy despite her similar hopes earlier. Her uneasiness increases one night at dinner when she tries to get to know him better. When she asks if he was ever married, he grabs her hand suddenly, jerking her toward him so she almost falls. He demands to know why she asked, and when she asks him to let go, he refuses to do so until she answers, finally pulling her until she falls. Flailing for balance, she inadvertently hits his face. He rebukes her for this, leaves and does not speak of it again.  Ann feels this is controlling, and decides his criticisms and orders were also controlling. Disturbed by his behavior, Ann begins to thinks of Loomis as a murderer and fears his horrible experiences have damaged his mind.
Some days later, Ann awakes at night to hear Loomis in her room. Fearing he heard her wake, she feigns sleep, hoping he will leave. But Loomis quietly approaches her bed, and brushes his hands over her, "not roughly, but in a dreadful possessive way", then puts his hand hard on her shoulder (to pin her down, she thinks). Ann ends her pretense and twists free as Loomis drops onto the bed. He grabs her leg blindly as she flees, pulls her backward and grabs her shirt as she struggles to escape. Ann elbows him in the throat and flees to the cave, where she hides in terror for some days, watching constantly, scared to sleep.
Ann then approaches Loomis from a safe distance to propose a compromise of sharing the valley and farm work but living apart. Loomis says he was hoping she would return. At first she thinks he is sorry and hopes to reconcile, but she feels she can no longer trust him. He professes surprise when she tells him she won't live with him anymore and asks why, as if he has no idea. Ann remembers that he acted the same after he had grabbed her hand, "as if nothing had happened, or as if he had forgotten it," She refuses to justify her choice to him, to tell him where she is living when he asks, or to come back to live with him. Loomis shrugs this off. She explains her proposal. Loomis answers that he has no choice but to accept, though he hopes she will reconsider and “act more like an adult and less like a schoolgirl". Ann tells him she won't change her mind. Though this arrangement is "unnatural and uneasy," and Ann worries about surviving winter, she sticks by her decision and wishes Loomis had never come.
About 10 days later, Loomis takes away the tractor key. When Ann asks for it to tend crops, he tells her if she continues to stay away, she will have to do without things. He then locks the store, which contains supplies she needs. Thinking he might have done so out of loneliness, Ann observes, "There are people who cannot stand being alone; perhaps he was acting from despair." She decides to offer to talk sometimes from a safe distance; but when she approaches the house, Loomis shoots her in the leg. Ann flees, expecting to be shot and killed, but he does not fire again. She realizes that he had not shot to kill, only to lame her to make her easy to capture. Loomis then uses her dog, Faro, to track her to the cave, where he burns her belongings, though Ann escapes. Ann's leg wound becomes infected. She hides in a hollow tree and has feverish dreams of another valley where children wait for her to teach them. Ann comes to believe the dreams are true and Loomis is insane, so she plans to steal the safe-suit and find her dream valley. Moreover, she decides to kill Faro to prevent Loomis from tracking her in the meantime, making her feel equally a murderer. Two weeks later, after Loomis tries to lure Ann to the store and wound her again, she tricks him in turn by leading Faro to a spot where she crosses stones spanning the dead creek. Hiding on the other side, she panics Loomis with gunfire so that he lets Faro go, to swim across the creek to Ann and become fatally poisoned.
In August, Ann acts on her plan. She lures Loomis from the house with a note offering to talk if he meets her unarmed in the south. She then steals the safe-suit, puts it on, and waits on Burden Hill for a last meeting. When Loomis arrives, enraged, he fires at the sound of Ann's voice, threatening to kill her if she doesn’t return the suit. She finally reveals knowing of Edward and despairingly invites Loomis to kill her the same way. Loomis is shocked by her knowledge of Edward's death, and stops threatening her. Becoming dispirited and meek, he says that Edward tried to steal the suit, like Ann. Seeming frightened and confused, he begs her not to leave him alone, saying, “It’s wrong.” After offering to send others to Loomis if she finds anyone, Ann complains that he never thanked her for nursing him; and, after these admittedly childish last words, she heads off into the deadness, expecting to be shot in the back. But Loomis' last action is to call out that he once saw birds circling to the west. Ann then walks most of the night until, exhausted, she sleeps. The next morning, she continues west beside a dead stream, hoping to see a green horizon.