The novel is narrated in the first person by a sixteen-year-old girl named Griet, who lives in the Dutch city of Delft. The story opens in the year 1664 when Griet is abruptly informed that she will be starting work as a maid in the home of the Dutch painter Vermeer and his wife Catharina. The economic situation of her own family has become precarious since her father, a tile-painter, was blinded in a workplace accident. Her brother Frans has begun an apprenticeship but is not yet earning any wages. Griet is reluctant to take on the position since her younger sister Agnes is angry with her for leaving, and because she is hesitant about working in a Catholic household. She understands, however, that she must help her family, and so she moves into her new home.
Vermeer and his wife have four daughters as well as an infant son, and Catharina is pregnant with another child at the time Griet is hired. The household also contains Catharina's mother, Maria Thins, and her maid Tanneke. Griet is tasked with a great deal of work, and there are also immediate interpersonal tensions. One of the children, Cornelia, clearly dislikes Griet and wants to make her life miserable; Catharina also seems to feel jealousy and resentment of Griet. This is exacerbated by the nature of one of the tasks Griet has been hired to perform. She is responsible for cleaning the studio where Vermeer works; it is extremely important to him that nothing be moved or altered in this room, and Griet must work very meticulously. Catharina, due to her clumsiness, is not permitted to enter the studio lest she unsettle something.
Despite these challenges, Griet is able to make herself indispensable in the household due to her shrewd bargaining and domestic management. Since she is responsible for purchasing meat for the family's meals, she begins to interact frequently with Pieter the butcher and his son Pieter the younger. The son is clearly attracted to her, but Griet is hesitant about encouraging these feelings. She experiences further unsettling feelings as her experience working at the Vermeer household makes her question her family's class position and their insistence on a Protestant faith. However, she begins to be exposed to a new world of challenging and exciting information through her interactions with Vermeer and his friend van Leeuwenhoek.
Two crises arise in the fall and winter of 1664. Plague breaks out in the neighborhood where Griet's family lives, and her sister Agnes falls ill and dies, permanently altering her family dynamic. Griet also catches the eye of Vermeer's wealthy patron van Ruijven, who is notoriously lecherous. Towards the end of the year, Catharina gives birth to a healthy son named Franciscus.
In early 1665, Griet takes on a new role in the household when she secretly begins to work as Vermeer's assistant, fetching supplies, grinding colors, and doing other tasks. She enjoys the work and the opportunity it gives her to learn from and interact with the painter, but keeping the work secret involves several deceptions and help from Maria Thins. Griet also becomes more confident about expressing her opinions and suggestions, which often impress Vermeer. The time spent with Vermeer also begins to foster an attraction towards him, but, unable to express her desire, Griet channels this attraction into her encounters with Pieter instead.
Catharina eventually becomes aware that Griet is assisting Vermeer, and reluctantly accepts this state of affairs. Indeed, Griet comes to occupy a position of some authority in the household. Tensions remain, however. Griet’s new identity within the Vermeer family increasingly creates a wedge between her and her parents. Pieter's plans for their future make her uncomfortable, as she cannot help but feel some repulsion due to his working class background and unfavorable contrast with Vermeer. Cornelia still seeks out opportunities to get her in trouble. And most dangerously, van Ruijven has not lost interest in Griet, and continues to insist on the possibility of posing for a painting alongside her. To avoid this, Vermeer reluctantly agrees to paint a portrait of Griet alone, which he begins early in 1666.
As Vermeer paints Griet's portrait in the winter months of 1666, the erotic tension between the two increases. Griet is terrified of what would happen if Catharina knew that her portrait was being painted, and she is also uncomfortable with van Ruijven's increasingly aggressive advances; however, she clings to the pleasure of interacting with Vermeer. The sexual awakening this triggers in her leads her to finally have sex with Pieter. As the portrait nears completion, Vermeer remains unsatisfied; ultimately, Griet and Vermeer realize that the portrait is in need of the inclusion of a piece of jewelry: namely, Catharina's pearl earrings.
Despite Griet's objections, Vermeer is insistent, and she pierces her ear in preparation for posing. On her eighteenth birthday, Maria tells her that Catharina has gone out for the day and that the session with the earring will take place while she is gone. She gives Griet the earrings and sends her upstairs; by this time, the attention of the girls has been attracted. As Griet starts to prepare to pose, she is interrupted by the news that she has a visitor. She goes outside to speak with Pieter, aware that Tanneke, the girls, and Vermeer are all watching from inside the house. She tries to delay, but Pieter insists on making his proposal of marriage. She tells him she will not discuss the question, and she hurries back to the studio.
Inside, Griet tells Vermeer to insert the earring for her, which he does. He then tells her she must wear the other one as well. Griet objects at first but then consents and pierces her other ear, wearing both earrings while he paints her. Afterwards, she returns the earrings to Maria to be replaced in the jewel box. Vermeer leaves the house, and Catharina comes home. A short time later, Griet realizes that Cornelia has led her mother upstairs to see the portrait. There is an outburst, and a message is sent for Vermeer to return home. Griet waits while he comes back and joins his wife in the studio. Cornelia then comes down and brings Griet up to the studio, where Catharina, Vermeer, and Maria are assembled. Catharina is furious and wants to know whether Griet has stolen the earrings that she is depicted wearing in the portrait. Neither Maria nor Vermeer speaks up to explain what really happened. Griet denies stealing the earrings, but also does not reveal the whole story.
Enraged, Catharina grabs a knife and tries to stab the painting, but Vermeer prevents her. As the pregnant Catharina becomes increasingly agitated, Griet realizes there is no future left for her in the house. She calmly walks out. Once outside, she considers the options for her future and makes a choice.
The narrative’s action resumes ten years later, in February 1676. Griet is now married to Pieter and works beside him at the butcher's stall. She is also the mother of two young sons. Her father has died, but her mother helps her to take care of the children. van Ruijven has also died. Vermeer has recently died, leaving behind Catharina and eleven children, as well as sizable debts. Over the years, Griet has had only sporadic contact with the family, mostly through Maertge. When she married Pieter, the Vermeer family abruptly switched butchers, leaving an unpaid bill of fifteen guilders. In part, they blame her for the loss of a child: on the day of the confrontation in the studio, Catharina went into premature labor, and the infant later died.
Unexpectedly, Tanneke seeks out Griet and asks her to come to the Vermeer house. Griet goes to the house later the day, and is met by some of the younger children. Franciscus comments on her being the lady in the painting. Confused, Griet asks about the whereabouts of her portrait. They explain that Van Ruijven’s daughter now owns it; however, on his deathbed, Vermeer asked for it to be loaned back to him. Maria greets Griet and sends her in to see Catharina and van Leeuwenhoek, who is the executor of Vermeer's will. They explain that before his death, Vermeer made a request, and Catharina is now going to honor it. Griet is shocked when Catharina gives her the pearl earrings; she tries to object, but she leaves with them. On the way out, Cornelia maliciously suggests that Griet give her the earrings; Griet slaps her.
When she leaves, Griet is unsure what to do with the earrings. She goes to a pawnshop and sells them, receiving twenty guilders in exchange. She gives fifteen to Pieter, explaining that Catharina has finally settled the debt. She hides the remaining five in a secret place, and never spends them.