In the Time of the Butterflies is divided into three sections of four chapters each. Each part opens with Dede in third-person narration whereas the narration is given in the first person for the other sisters. Dede’s chapters are divided into two parts: 1994 (the present) and the past, when her sisters were alive, beginning with 1943. The time frame of the "present" is a span of one afternoon, in which Dede gives an interview. But the interviewer’s questions transport Dede, and the reader, back in time and into the consciousnesses of the sisters.
Dede begins an interview with a woman at around three o'clock. It is 1994. When Dede asks her what she wants to know, the interviewer answers, "Tell me all of it." Dede is transported back to 1943, to "a clear moonlit night before the future began." The whole family is out in the front yard under the anacahuita tree, relaxing and telling stories.
In 1938, Patria and Minerva go to Inmaculada Concepcion as boarding students. Minerva meets Sinita Perozo, who tells her how Trujillo destroyed her family—killing her uncles, her father, and her brother. Minerva considers, for the first time, that Trujillo is not the saint he makes himself out to be. This realization is driven home when in 1941, her friend Lina Lovaton is chosen to be one of Trujillo's mistresses, destroying her chance at having a fulfilling life. Minerva and her friends are chosen to give a recitation performance for Trujillo at the centennial celebration, but it ends disastrously when Sinita breaks from the script and walks toward Trujillo's chair, taking aim at him.
Maria Teresa has received a diary from Minerva for her First Communion. Patria has gotten married and given birth to two children, Noris and Nelson, and is pregnant with a third. Maria Teresa begins school at Inmaculada Concepcion, where she chooses to lie for Minerva, who has been sneaking out of school to meet secretly with her friends at Don Horacio's house. One of those friends, Hilda, hides at Inmaculada Concepcion, pretending to be a student, but soon she is captured by guards. In July, Minerva graduates and Patria miscarries, losing her son.
In 1946, Patria is 22 years old and, despite always believing she would end up becoming a nun, has chosen to marry Pedrito Gonzales. She is worried about Minerva, who is speaking out against the government. In worrying about Minerva's loss of faith, she herself begins to struggle with her faith. After the miscarriage of Patria's third child, Chea Mirabal decides to take all her daughters on a pilgrimage to Higuey, where it is revealed that Enrique Mirabal is unfaithful to her.
Back in the present, in 1994, Dede considers that Fela, their longtime servant, thinks that she is possessed by the spirits of the dead Mirabal sisters. The interviewer reminds her about Lio Morales, whom Dede and Minerva met one summer and subsequently invited to play volleyball at Tio Pepe's. When a newspaper that reports that Lio is "a communist, a subversive," Mama becomes upset that she has been letting him spend time at their home. Although she denies being in love with him, Minerva continues to see him—on double dates with Jaimito and Dede. On the night that Jaimito proposes to Dede, Lio gives her a letter to deliver to Minerva, asking Minerva to go into exile with him and his comrades. Dede decides that she will not expose her sister to that danger, so she burns the letter in the lamp.
After graduating from Inmaculada Concepcion, Minerva has been living at home for a few years. She accidentally discovers Carmen, the woman with whom her father has been having an affair, and her four half-sisters. She also discovers four letters from Lio, which her father has been hiding from her. The family is invited to a Discovery Day dance at one of Trujillo's palaces; Manuel de Moya tries to seduce Minerva, and when Trujillo touches her inappropriately, she slaps the dictator in the face. When he pulls her inappropriately close, thrusting at her in a vulgar way, she slaps his face. A rainstorm begins, and the Mirabals escape; but on the ride home, Minerva realizes that she has put the letters from Lio in the pocket of the lining of her purse, which she left at the palace. Enrique Mirabal is sent to the capital for "questioning," and while he is there Minerva brings money to his illegitimate family. Minerva and Chea Mirabal go to the capital to petition for Papa's release. He is released after three weeks, but he has gone insane. In their meeting with Trujillo, Minerva makes a bet with the dictator; she wins, and he allows her to study law.
Maria Teresa has a new journal, which is another gift from Minerva. Enrique Mirabal has passed away, and Maria Teresa mourns his death, but she also has developed crushes on both of her cousins, Raul and Berto. On July 3, Maria Teresa graduates from Inmaculada Concepcion, and in September, she joins Minerva at the university in the capital, and they are roommates. Minerva marries Manolo in 1955, so she moves in with him. Soon, she gives birth to Minou, and in 1957, they move to Monte Cristi.
Trujillo plays a terrible trick on Minerva by not actually granting her a license to practice law; her diploma is useless. Maria Teresa helps Minerva set up her new home in Monte Cristi. She accidentally intercepts a delivery of guns from Leandro, codename Palomino, to the house. Manolo and Minerva explain about the national underground that is forming. Maria Teresa joins them and begins to fall in love with Leandro, whom she marries on Valentine's Day, 1958.
It is now 1959 and Patria's children, Nelson and Noris, have grown up. They all live in Pedrito's great-grandfather's house. Minerva and Manolo visit from Monte Cristi every week; they meet on Patria and Pedrito's land with many other revolutionaries. This situation gives Nelson the chance to get involved when he is home from school. He reports back to her that the revolutionaries are expecting an invasion by the liberators from Cuba.
Though she is pregnant with Raul Ernesto, Patria decides to go on a retreat with Padre de Jesus and the Salcedo group to Constanza. On the fourteenth of June, the mountainside is bombed. The first wave of the liberating invasion is the target; six days later the second wave is intercepted and also defeated. Padre de Jesus changes the name of the retreat group to Accion Clero-Cultural, or ACC. Though Pedrito protests at first, the Fourteenth of June Movement is founded in Patria and Pedrito's home.
In the afternoon in 1994, Dede says goodbye to the interviewer just as Minou arrives from Fela's. Back in 1960, Dede has become solitary and feels that Jaimito has become a "bossy, old-fashioned macho" who doesn't notice her unhappiness. Her sisters come to ask her to join their revolutionary cell, and Dede silently decides to leave Jaimito. She is about to ask the priest for advice, but when she realizes that Padre de Jesus is "one of them," she becomes afraid he will convince her to join the revolution, so she flees. Jaimito has left her with his sons, but Manolo convinces them to reconcile and take a vacation together. The next week, Leandro, Pedrito, and Nelson are arrested, and Patria's home has been burned to the ground. Minerva has tuberculosis, but she and Manolo are also arrested before she can get treatment. Dede and Jaimito are able to rebuild some strength in their marriage in their effort to save her sisters.
For three months, Patria stays at her mother's house suffering without her son, husband, or Minerva. Soon, Maria Teresa is also arrested. The Catholic Church speaks out against the regime, and the regime fights back by finding ways to dissuade people from attending church. Through Margarita, one of Enrique Mirabal's illegitimate daughters, Patria and Chea are able to communicate with Minerva and Maria Teresa in La Victoria prison. Captain Pena comes to Chea Mirabal's house with visiting passes, reporting that Nelson might be released with the next round of pardons. But Minerva and Maria Teresa have refused their own pardons. On the next Tuesday, they drive to the capital to pick up Nelson.
In jail at La Victoria, Maria Teresa writes in a smuggled notebook from Carmen's cousin Santiclo, who is one of the guards at La Victoria. On April 11, Maria Teresa is taken to La 40 and whipped in front of Leandro, to try to convince him to do a job for Trujillo, though it is not described what the job is. It works; Leandro cries out, "I'll do it! I'll do it!" On Monday, May 23, Maria Teresa and Minerva are arraigned and sentenced to five years in prison at a "joke of a trial," having no legal representation. The Organization of American States (OAS) is coming to investigate the political prisoners' situation, and Minerva urges Maria Teresa to share with the OAS the incident she has written down. After her ten-minute session in the visitors' hall with seven members of the committee, Maria Teresa lets the letter containing the statement written by Minerva and Sina and signed "The Fourteenth of June Movement" fall out of her braid, and the young commissioner leading her out picks it up. However, she does not let drop the letter with her own personal account. On August 7, Maria Teresa reports that she and Minerva will be released the next day along with the other female political prisoners.
Minerva and Maria Teresa have been released but are now on house arrest. To make money, they start up a specialty business of making children's christening gowns. In prison, Manolo's spirits are crushed when a group of young men is caught distributing revolutionary leaflets in Santiago. Delia Santos tells Minerva to visit Dr. Pedro Vinas, who explains that the "gringos" are helping with the revolution. Manolo fears, however, that they will also take over the country. Minerva loses the house she owns with Manolo, and Dede helps her organize and clean it out. The next Thursday, while they are on the way to visit their husbands, Captain Pena tells them that Manolo and Leandro are being transferred to Puerto Plata, nearer to where the sisters live. On November 25, on the way to Puerto Plata, the sisters' driver, Rufino, decides to stop and pick up a young soldier who is hitchhiking.
The sisters stop at a store called El Gallo on the way to Puerto Plata to buy sewing supplies for their company. The salesclerk, Jorge Almonte, recognizes them and gives Minerva a written warning to "Avoid the pass." But there is nothing to be done, so they keep driving. Nevertheless, they safely arrive at Puerto Plata and visit Leandro and Manolo, who asks Minerva not to drive back that night. After failing to get in touch with their mother by phone, they decide to head home.