In 1660 on Martha’s Vineyard in the settlement of Great Harbor, fifteen-year-old Bethia Mayfield lives with her pastor father; her brother, Makepeace; and her sister, Solace. Her mother died in childbirth, along with the unnamed baby. Bethia most misses her twin brother, Zuriel, who died in an accident. Resisting the female role that is expected of a Puritan girl of that time, Bethia listened as her father taught Zuriel. When she was forced from the house, Bethia continued to study in secret. Her love of learning is her secret sin.

Outdoors, she wanders the island and encounters the Wampanoag, the island’s first inhabitants. She makes friends with one, who is later called Caleb, though she must keep their friendship a secret. Bethia is bothered by the lack of respect the colonists show toward nature. She is more captivated by the spiritual life of the Wampanoag than by her father’s preaching on the Sabbath.

As Bethia becomes closer to Caleb, she reveals to him her understanding of God. Caleb is confused, but he is interested in her ability to read of past wisdom from a book. He tells Bethia to give him the book she is reading, but Bethia explains it is not hers to give; it belongs to her father. Caleb, like the other Wampanoag, has no understanding of personal property and becomes angry. Bethia promises to bring him her catechism and hopes she can introduce him to Christianity. Bethia feels confused by some of Caleb’s questions, so she asks her father to take her with him when he goes to preach to the Wampanoag. He readily agrees, but Bethia overhears the Wampanoag question his teaching. When Tequamuck, Caleb’s uncle, arrives, all the Wampanoag leave silently.

Caleb announces to Bethia that he will not see her anymore; he is to undergo a trial by ordeal. Bethia feels heartbroken and fearful of Caleb’s fate. She learns that her father is considering marrying her to Noah Merry, a young farmer nearby. When Pastor Mayfield visits the Merrys, Bethia’s mother urges her to go along. While there, two natives arrive to tell of a visitor at their village who is ill. Bethia and her father journey there and discover Caleb’s father, who has taken hellebore in order to have visions. As Pastor Mayfield tends to him, Bethia takes some of the hellebore and has wild hallucinations. Afterward, she sees this as evidence that she is one of those condemned by God from birth.

Caleb’s father is healed, and Pastor Mayfield hopes this will help him reach them. But Tequamuck stops them. Later, Caleb’s father and many others of the tribe die from small pox. Pastor Mayfield announces that Caleb will come to live with them and learn along with Makepeace and Joel, another Wampanoag who has converted to Christianity; he may later go to the Indian School at Harvard. Bethia is unsettled by Caleb’s close presence but focuses on her chores. She sees dedication to the household tasks as a way to atone for her sins, which she believes contributed to her mother’s death. Makepeace doubts Caleb’s conversion and believes he is still an “idolater.”

Bethia devotes herself to her baby sister, Solace, and is heartbroken when the baby drowns in a newly dug well. Pastor Mayfield deals with his grief by preaching more of hell than of heaven. He is convinced that the only way to make headway in the conversion of the Wampanoag is to destroy the power of their pawaaws (medicine men). He decides he needs help from England, as John Eliot did for his mission to the Indians on the mainland. Pastor Mayfield leaves for England but is drowned when his ship sinks in a storm.

Tequamuck, the Wampanoag pawaaw and Caleb’s uncle, cursed Mayfield at his departing, so Makepeace blames him for his father’s death and wants him held accountable. Makepeace becomes suspicious and jealous of Caleb and even accuses Bethia of secretly lusting after him. Bethia and Makepeace’s relationship begins to break down.

Grandfather Mayfield, who is magistrate of Great Harbor, informs Makepeace that the money saved for his college has been used up in sending Pastor Mayfield to England. Makepeace is not academically ready for Harvard, so he will have to go to a preparatory school in Cambridge run by Master Corlett. Corlett agrees to take Makepeace if Bethia will be indentured to him for four years. Caleb is furious that Bethia is sold to benefit Makepeace, but Bethia believes it is an opportunity sent by God. When Bethia arrives at Cambridge, Corlett explains that he is widowed and no local women will serve because of the Indian boys, but he wants the influence of a gentlewoman such as Bethia. He assures Bethia that she will not be treated like a drudge. When the son of the governor treats her like a lowly servant, Caleb corrects him and he apologizes. Bethia is interested to learn that Corlett’s sister is Anne Bradstreet, the poet.

Master Corlett informs Bethia that he is taking on another Indian student under unusual circumstances. Governor Dudley has a protégée called Anne, whom he rescued from harsh treatment.  When she arrives, she is frightened and responds only to Bethia, who begins her on lessons in Latin, some of which she already knows.

Makepeace confesses to Bethia that he cannot keep up academically and will not pass. He intends to quit and tells her that, for her own sake, he has written Noah Merry that he consents to Bethia’s marriage to him without delay. Noah will pay off the indentured fees. Bethia is horrified and swears at Makepeace, who informs Master Corlett of her blasphemy. Rather than involve the courts, Corlett allows Makepeace to beat Bethia, who then must publicly confess to her crime.

Master Corlett approaches Bethia about her coming departure, and she tells him that she does not want to marry Noah. Master Corlett says he is not legally bound to accept payment for her indenturement and will not if she chooses to stay. He presents her with the option of marriage to his son, Samuel, who was impressed with her at her public confession. Bethia wonders how her disgrace could raise Samuel’s impression of her and agrees to meet him. As Bethia comes to know him and as they discuss literature and the sciences, she appreciates his respect for her mind. She cannot decide whether it is better to marry a poor man who respects her intelligence or to marry a man who has financial security on the island she loves.

When Samuel proposes marriage to her, they are interrupted by news of Anne’s miscarriage of a baby than no one knew about. The midwife spreads the suspicion that Caleb or Joel is the father, but Bethia is sure, from the size of the fetus, that Anne was pregnant before she came to Cambridge, which means the child was conceived while she lived with the governor. Master Corlett knows he cannot accuse the governor of this.

While Bethia struggles to decide what to do, Noah Merry arrives with the news that he has fallen in love with someone else and releases Bethia from their engagement. He also gives her the indenture papers, having paid the debt himself. Noah is heading back immediately to Martha’s Vineyard and agrees to take Anne back secretly and situate her with a tribe near his home but far from Great Harbor. When Makepeace announces that he will go back with Noah, Bethia tells him about Anne, and Makepeace agrees to keep quiet about this.

When Samuel discovers Bethia’s involvement, he is furious at her headstrong attitude, yet he still loves her and tells her so. Caleb is incensed that there is no justice for Anne, and a few days later, the governor’s son mysteriously dies. Bethia convinces Samuel to wait for six months before deciding on an engagement. Bethia takes a job at Harvard working in the buttery, where she can overhear President Chauncy’s lectures.

After six months, Samuel renews his marriage proposal, and Bethia accepts. After they are married, they travel to Padua, Italy, where Samuel becomes a teacher in the medical school at the University of Padua. After two years, they are called home due to Master Corlett’s ill health. On their return, Bethia gives birth to her only child, a boy whom they name Ammi Ruhama.

Caleb and Joel suffer through the torment of their freshman year and eventually complete all four years; Joel becomes valedictorian. Before the ceremony, however, he travels back to Martha’s Vineyard and marries Anne. On the way back to Cambridge, he is shipwrecked on an island and murdered by the inhabitants. At the graduation ceremony, Caleb refuses the honor of addressing the graduates. Afterward, Bethia sees him behind a tree, coughing into his handkerchief.

Caleb has contracted consumption. Bethia cares for him at the home of Thomas Danforth in Charlestown. Bethia feels desperate for some way to help, so she returns to Nantucket and seeks aid from Tequamuck. She returns to Caleb’s bedside and whispers the verses given to her by Tequamuck. Caleb sings his death song and dies.

Bethia and Samuel return to Martha’s Vineyard some years later to escape the violence of King Philip’s War. Ammi Ruhama marries Noah Merry’s daughter and has several children. When Bethia dies in 1715, she is living with her son and tended by her grandchildren and great-grandchildren. She finishes writing the story of her life, begun long ago in her childhood. She sees it not as her death song but as a lament.