The narrator introduces Aylmer, a brilliant yet lonely scientist who is "proficient in every natural branch of philosophy" (Hawthorne 152). Aylmer abandons his scientific endeavors to pursue and marry the beautiful, sweet-natured Georgiana. One day, Aylmer gazes at his wife and asks her if she’s ever considered removing the red hand-shaped birthmark on her cheek. Georgiana tells him no, as most men have found the birthmark charming. Aylmer expresses his dissatisfaction with the birthmark, reasoning that Georgiana’s face is near perfection, so any blemish, mark, or physical flaw downright shocks him. Georgiana is initially angered by Aylmer’s callousness, but she soon resents and obsesses over the mark just as her husband does. Her self-confidence shatters, and she becomes repulsed by her own appearance.
As the birthmark continues to preoccupy Georgiana and Aylmer’s minds, their marriage begins to fall apart. One night, Georgiana reminds Aylmer of one of his dreams; she recalls him exclaiming "It is in her heart now; we must have it out!" aloud while he slept (154). Aylmer then remembers that he dreamed about surgically removing his wife’s birthmark with a knife. This proved to be a difficult task: as Aylmer cut deeper and deeper, the birthmark followed until it became part of Georgiana’s own heart. Upset, Georgiana tells Aylmer that she wants to have the "fatal birthmark" erased regardless of the consequences, which, according to her, could include a deformity or even death (155). Aylmer enthusiastically agrees to try to eliminate the mark. He proceeds to bolster his own scientific abilities and intellect, even comparing himself to Pygmalion.
The couple then moves to Aylmer's apartments, which occupy his laboratory. Georgiana faints as she enters her husband’s lab. Aylmer calls his assistant, the grotesque and stocky Aminadab, for help. As Aminadab gazes at Georgiana, he mutters, "If she [Georgiana] were my wife, I'd never part with that birthmark" (157).
Georgina wakes up in a beautiful room in her husband’s laboratory. To cheer her up, Aylmer shows her some of his creations and hands her a pile of dirt. Right before their eyes, the dirt rapidly grows into a blossoming plant, which dies as soon as Georgiana touches it. Aylmer then attempts to create a portrait of Georgiana with a plate of metal (in a process akin to early photography), but the image turns out blurry, with a prominent exception being the hand shape of Georgiana’s birthmark. Angered, Aylmer throws the plate into a jar of acid.
In between studying and his experiments, Aylmer visits Georgiana and tells her about alchemy, the early branch of science intended to transform everyday objects and metals into gold. Aylmer believes that he himself could perform alchemy, and, in turn, conjure an elixir vitae, a potion with the power to indefinitely prolong the life of the drinker. Aylmer acknowledges the immorality involved in the creation of the potion—it would be a violation of Nature and a selfish, corrupt pursuit for domination. He reassures Georgiana, telling her that he won’t chase after such power.
Later, Aylmer shows Georgina his current experiments, potions, and poisons, including a perfume "capable of impregnating all the breezes that blow across a kingdom" (159). Among the most potent of his collection, though, is a golden liquid poison deemed "the elixir of immortality" by Aylmer (159). The poison has the potential to kill an individual instantly or gradually. Aylmer then shows a horrified Georgiana a "powerful cosmetic" that can erase freckles, though he admits her birthmark will require a more powerful solution to fade (160).
While her husband works, Georgiana reads the philosophical books in Aylmer’s study. She devours Aylmer’s accounts of his own scientific experiments and finds out that most of her husband’s achievements have failed to meet his expectations and goals. For Georgiana, this discovery of Aylmer’s humane imperfections only makes Georgiana love, respect, and worship him more.
Later, Georgiana follows her husband into his laboratory. Enraged, Aylmer commands her to leave. Georgiana refuses and instead urges him to tell her about the current progress of his experiment. She then claims that she will submit to Aylmer and drink whatever "draught you bring me" (163). Impressed, Aylmer admits that the sole option available to erase the mark remains dangerous. He then encourages Georgiana to decompress in her boudoir, where she proceeds to fondly think of her husband and his determination to change her.
An anxious Aylmer enters Georgiana’s room with a colorless liquid and assures her "it [the potion] cannot fail" (163). To demonstrate the power of the solution to Georgiana, Aylmer uses it to erase yellow blotches on a geranium. Georgiana proceeds to drink the liquid, declares it to be delicious, and falls asleep. Aylmer observes her anxiously yet tenderly, and, eventually, the birthmark fades. Aminadab laughs, and Aylmer’s triumphant exclamations about the experiment’s success awake Georgiana. She gazes into the mirror and tells Aylmer, "you have aimed loftily; you have done nobly. Do not repent that with so high and pure a feeling, you have rejected the best the earth could offer" (165). Georgiana dies moments later.