The narrator introduces Aylmer as a brilliant scientist and natural philosopher who has abandoned his experiments for a while to marry the beautiful Georgiana. One day, Aylmer asks his wife whether she has ever thought about removing the birthmark on her cheek. She cheerfully says no but grows serious when she sees that he asked the question seriously. Many people, she says, have told her the mark is a charm, and she has always thought maybe they were right. Aylmer says that because her face is almost perfect, any mark is shocking. Georgiana is angry at first, and then she weeps, asking how he can love her if she is shocking to him.
The narrator explains that the birthmark in question is a red mark in the shape of a tiny hand on Georgiana’s left cheek. The mark disappears when she blushes. Georgiana’s male admirers love the birthmark, and many would risk their lives just to kiss it. Some women think the mark ruins her beauty, but the narrator says this is nonsense.
Aylmer obsesses about the birthmark. For him, it symbolizes mortality and sin and comes to tower over Georgiana’s beauty in his mind. He can think of nothing else. One night she reminds him of a dream he had. He spoke in his sleep, saying they must take out her heart. Aylmer remembers dreaming that he had removed the birthmark with a knife, plunging down until he had reached his wife’s heart, which he decided to cut out. Georgiana says that she will risk her life to have the birthmark erased. Thrilled, Aylmer agrees to try. He professes complete confidence in his own abilities, likening himself to Pygmalion. He kisses his wife’s unmarked cheek.
They decide to move to the apartments where Aylmer has his laboratory. He has already made stunning discoveries about volcanoes, fountains, mines, and other natural wonders. Now he will resume his studies of the creation of life. As the couple enters the laboratory, Aylmer shudders at the sight of Georgiana, and she faints. Aminadab, Aylmer’s grotesque assistant, comes out to help. He says he would not remove the birthmark if Georgiana were his wife.
Georgiana wakes up in sweet-smelling rooms that have been made beautiful for her. Aylmer comforts her with some of his more magical creations: “airy figures, absolute bodiless ideas, and forms of unsubstantial beauty.” He shows her moving scenes that mimic real life. Then he gives her a fast-growing flower that dies as soon as she touches it. Next he tries to create a portrait of her with a metal plate, but when the plate shows a hand, he throws it into acid.
Between experiments, Aylmer tells Georgiana about alchemy. He believes that he could turn base metal into gold and create a potion that would grant eternal life if he wanted to, even though he says he knows that doing so would be wrong. He disappears for hours and then shows her his cabinet of wonders. One such wonder is a vial that holds a powerful perfume. Another is a poison that, depending on the dose, would allow Aylmer to kill someone instantly or after a long period of time. Georgiana is appalled, but Aylmer says the poison is more good than bad. He shows her another potion that can wipe away freckles, but he says her birthmark needs a much deeper cure.
Georgiana realizes that Aylmer has been doctoring her food or making her inhale something in the air. Her body feels strange. She reads the books in his scientific library, as well as his accounts of his own experiments. She realizes that his achievements always fall short of the goals he originally sets. Still, the accounts of his studies make her worship him. Aylmer catches her crying over his journals, and although his words are kind, he is angry. She sings to him, restoring his spirits.
A few hours later, Georgiana goes to the laboratory to find Aylmer. When he sees her, he grows angry, accuses her of prying, and tells her to go away. She stands her ground and refuses, saying he should trust her and not try to hide his fears. She promises to drink whatever he tells her to drink. Moved, Aylmer says the mark goes deep into her body, and its removal will be dangerous. In her room, Georgiana thinks about how noble it is that Aylmer refuses to love her as she is, insisting instead to create his ideal version of her.
He brings her a potion that he says cannot fail. He shows her how it cures a geranium of blots. She drinks the liquid and sleeps. Aylmer watches her with tenderness but also as if he is watching a scientific experiment unfold. Gradually the birthmark fades. Aminadab laughs. Georgiana wakes, sees herself in the mirror, and tells Aylmer not to feel bad about rejecting “the best the earth could offer.” Then she dies.