Sixteen-year-old Ethan Wate lives in Gatlin, S.C., but dislikes his small town and would like to move away. He lives with his father and a housekeeper; his mother has passed away.
On the first day of his sophomore year of high school, Ethan again has a dream about falling through mud with a girl whose face he can't see. This dream has been recurring for months, and it troubles Ethan because in the dream he loves the girl he is falling with, though he does not know who she is. When Ethan wakes, he finds a new song by an unknown artist on his iPod. The song is called "Sixteen Moons," and the lyrics seem eerie to Ethan. When he checks his music player later, the song is missing.
When Ethan arrives at school, he hears about a new girl in town, Lena Duchannes. Lena is ignored by most of the students because she wears long dresses and is not interested in popular pursuits like trying out for the cheerleading squad. Ethan hears Lena playing the song "Sixteen Moons" on her viola in band, which unsettles him. Ethan drives away from school to clear his mind, and he hears "Sixteen Moons" playing over his car radio. As Ethan drives, he nearly runs over Lena. When he stops his car, he suddenly realizes that Lena is the girl who appears in his nightmares. Lena accepts a ride home from Ethan, which marks the start of their friendship.
In English class the next day, Ethan begins to hear Lena communicating with him telepathically. The girls in class insult Lena's reclusive uncle, Macon Ravenwood, and Lena's anger affects the classroom, shattering the glass in the windows. Lena runs home to Ravenwood Manor, and Ethan follows her. Lena is crying in a garden full of lemon trees, and she begins to talk with Ethan. She says that sometimes unexplainable things happen around her. Suddenly, Ethan touches an old locket that is sitting on the ground, and he begins to see a vision of the past. In the vision, a girl named Genevieve is watching her mother's plantation, Greenbrier, burn down. This happens during the time period surrounding the Civil War. Lena is interested in Ethan's vision, but she cryptically warns him that her life is complicated and that he should not try to interact with her again.
Ethan keeps the old locket with him and asks his three great aunts, known as the Sisters, about it. The Sisters tell him that the locket comes from the year when General Sherman burned every plantation in Gatlin, except for Ravenwood Manor. The Sisters identify the two sets of initials, which are carved into the locket, as belonging to an ancestor of Lena's — Genevieve Duchannes — and an ancestor of Ethan's named Ethan Carter Wate. In church, Ethan touches the locket and has another vision of Genevieve Duchannes talking with her fiancé, Ethan Carter Wate. That night, Ethan has another dream of Lena slipping away from him, and he dreams he was drowning and wakes up soaking wet.
After Lena misses a day of school, Ethan visits her house and meets her Uncle Macon Ravenwood, a man who no one in Gatlin has seen for years. Macon does not want to give Ethan additional information about the locket, and Ethan notices that the interior of Ravenwood Manor seems to be magical, because the interior decoration can change and entire meals can appear and vanish, seemingly according to Macon's will.
That night, Lena comes to Ethan's house and sneaks into his room to explain her unusual family. She says that all the people in her family are Casters (spell casters) who have special powers. Despite this revelation, Ethan's attraction to Lena grows, and he asks her to go on a movie date with him. They hold hands at the movie theater, which sparks rumors about Ethan and Lena at their high school.
Ethan soon meets Lena's older cousin Ridley, a seductively dressed and very persuasive girl. Ridley invites Ethan to the Gathering, a holiday dinner held by Lena's extended family every year. Ridley reveals that in five months, Lena will turn 16, and on 16th birthdays, all members of the Duchannes family are Claimed as either Light Casters or Dark Casters. After the dinner, Ethan sits in Lena's bedroom as Lena explains that Ridley is a Siren, a Dark Caster with the ability to persuade people to do anything she wants. Lena is afraid that she will become evil as Ridley is and be claimed as Dark on her upcoming birthday. Ethan assures her that will not happen, and he kisses Lena for the first time.
That night, Ethan wakes up and sees that his housekeeper, Amma, leaving the house. Ethan follows Amma to her own home, where he watches as she goes out to the swamp and meets Lena's uncle, Macon Ravenwood. Macon is upset that Amma has not stopped Ethan from meeting with Lena, as it could be dangerous for both teenagers. Amma and Macon have questions they want to ask the ghosts of Amma's relatives, whom she refers to as the Greats. The ghosts are uncommunicative, and Macon and Amma are unaware of Ethan's presence at their meeting.
The next day, Lena and Ethan skip school and touch the locket again. This time, they see a vision of Genevieve Duchannes tending Ethan Carter Wate's bullet wound just before he dies. They go to the Gatlin County Library to get information from Marian Ashcroft , a librarian who was Ethan's mother's best friend. At the library, they have one more vision of Genevieve trying to bring Ethan Carter Wate back to life by using a magical text called the Book of Moons. Marian Ashcroft reveals herself to be a Keeper, a mortal who knows about the Light and Dark Casters and keeps a record of their doings. There is a secret part of the Gatlin Library known as the Caster Library, and Lena thinks this place may contain the Book of Moons. However, in order to search for the book, Lena and Ethan must wait for the Caster Library to open, according to its own magical schedule.
On Halloween night, Ethan wakes up from a vision that Lena is in trouble. He drives to Ravenwood Manor and goes inside to find Lena lying on a table, with most of her family members standing around her. Lena is in pain, and her family is reciting a Latin chant to stop a spiritual attack on Lena by a Dark Caster named Sarafine. Ethan's presence seems to break the spell, and Macon's mother, Arelia, concludes that Ethan's love is the only force that can protect Lena from the schemes of Sarafine.
On Thanksgiving, Amma invites Lena to Thanksgiving dinner with the Wate family. Amma uses magic to suspend time so she and Lena can talk to each other while the family sits by, frozen and unaware. Ethan can overhear their conversation, as Amma tells Lena that Sarafine is actually her mother.
Ethan and Lena go to the Caster Library. In the library, they touch Genevieve's locket again and discover the source of the curse on the Duchannes family of Casters. Genevieve used the Book of Moons to work dark magic and bring Ethan Carter Wate back to life, and the Book gained the power to choose which of the Duchannes children would go Dark or Light in the future. In the library, Lena faints and is again spiritually attacked by Sarafine, but she wakes up when Ethan kisses her. Ethan and Lena need to find the Book of Moons, and they think it might have been buried with Genevieve. They go to Genevieve's grave and dig up the book. Then they study it to see if they can find a way to keep Lena from becoming Dark.
At Gatlin High's winter formal, some of the girls ruin Lena's dress by pouring liquid soap on her and Ethan. Lena's cousin Ridley arrives at the formal and takes revenge for Lena's humiliation by mentally turning on the sprinkler system in the school. The water ruins the dresses of all the girls who were mean to Lena, causing chaos. The mothers of the mean girls believe Lena is responsible for the incident, and they sign a petition to have Lena expelled from school. The school principal holds a hearing and is about to expel Lena when Macon arrives to protest the hearing. Lena is allowed to return to school.
Over Christmas break, Ethan discovers that his reclusive father, Mitchell Wate, has not been working on his novel for the past several months. He has been sitting in his study, grieving for his dead wife. In Mitchell's study, Ethan and Lena notice that several books are open to certain pages, and the pages refuse to be turned. Some magical influence is spelling out a code in the books, and the message tells Lena, Claim yourself. Lena and Ethan continue to search through the Book of Moons, looking for a magical option that will allow Lena to choose her own fate.
The day of Lena's 16th birthday, Ethan goes to Ravenwood Manor to see her. Her extended family of Light Casters is with her. Lena is surprised when her Dark Caster cousin Ridley comes to the house with Ethan's best friend, Link, and several other students from the high school. Ridley has put a verbal spell on the students who used to be mean to Lena so that they will treat her nicely on her birthday. Other students are setting up a big party for Lena in the field outside of Ravenwood. Macon forbids Lena to attend the party because of the potential dangers, but Lena sneaks out to enjoy the festivities anyway. Lena and Ethan dance together and finally say that they love each other.
Ethan has to leave the party when he hears that his father, Mitchell, is standing on the balcony of a local museum, and appears as if he is going to jump. Ridley has nearly persuaded Mitchell to take his own life, but Link convinces her to release Mitchell from her spell. Ridley reveals that this was a plot to lure Ethan away from Lena, since his love is her main protection from Sarafine. Ethan and Link head back to Ravenwood Manor and meet Link's mother, Mrs. Lincoln, on the way. Ethan discovers that the woman is not Mrs. Lincoln, but the Dark Caster Sarafine in disguise.
Sarafine tells Lena that she will be able to Claim her own self for the Dark or Light at midnight. Lena's choice is a complicated one: If she chooses to go Dark, all the Light Casters in her family will die. If she chooses to go Light, all the Dark Casters in her family will die, including Uncle Macon. Sarafine's fellow Dark Casters attack and kill Macon, and Ethan runs to Ravenwood Manor to get help. After gathering the Light Casters, Ethan runs to find Lena in the woods, but instead meets Sarafine, who stabs him in the stomach with a knife.
From Lena's point-of-view, midnight strikes, and she sees her mother stab Ethan. Sarafine flees, and Amma arrives with the Book of Moons to help advise Lena. Lena and Amma recite a spell to bring Ethan back to life, and it works. Lena uses her power over nature to block out the moon at midnight, which keeps her from being claimed at all, either for Dark or Light. In the days after Macon's death, Ethan hears a new song called "Seventeen Moons" playing on his iPod, and he knows that the fight between Light and Dark Casters is not yet over.