In 1959, evangelical Baptist preacher Nathan Price takes his family to the Belgian Congo as missionaries. Nathan travels to Africa intent upon saving souls, but his wife, Orleanna, and four daughters (Rachel, Leah, Adah, and Ruth May) are more concerned with what supplies they should take to live comfortably there for the next year. When they arrive in the Congo, they are assigned to the village of Kilanga, where the Prices will be the only American family. Soon after their arrival, it becomes clear that they brought the wrong types of supplies and are woefully unprepared to deal with life in such a drastically different culture and climate. Nathan is inflexible in his approach to both the Congolese and his family, and Orleanna and her daughters are overwhelmed by their changed circumstances.
In time, the Price girls begin to adjust to their new life in the Congo. Rachel hates everything about it and simply wants to be a normal American teenager. Leah, Adah, and Ruth May, on the other hand, begin to appreciate the Congo. Leah, who is Adah's twin, enjoys observing the Congolese culture, while Adah studies the variety of plants, animals, and insects around them. Ruth May spends her time climbing trees and befriending the village children, to whom she teaches the game, "Mother, May I?" Meanwhile, Nathan tries to persuade the villagers to come to church and get baptized, and Orleanna worries for her family's safety and health.
The stability of the Prices' mission in Kilanga is soon challenged on both local and global fronts. One night Anatole, the schoolteacher, comes to dinner and tells the family that the village chief is unhappy with Nathan's church. Rather than trying to work out a compromise with the chief, Nathan gets angry and sends Anatole away. Around the same time, Ruth May breaks her arm, and Nathan takes her to a doctor in Stanleyville. While there, the doctor discusses the possibility of the Congo gaining independence, and Nathan scoffs at the idea. Soon after, the Underdowns (missionaries who once served in Kilanga) tell the Prices they need to leave the Congo due to the upcoming elections and independence, but Nathan refuses, determined to continue his mission.
Orleanna and Ruth May become sick and are bedridden. With their mother ill, Rachel, Leah, and Adah must now run the house, and they soon discover just how difficult it is. After a month of illness, Orleanna is well enough to get around again, but Ruth May doesn't show any signs of getting better. Orleanna begins actively searching for ways to get her family out of the Congo.
During this time, the area enters a period of drought, compounding the difficulties in finding food. Seeing that the Prices are struggling to keep their family fed, Tata Ndu, the chief, begins courting Rachel, intent on marrying her in order to give the Prices one less mouth to feed. Although the Prices appreciate the intention, they don't want Rachel to marry the chief, but they also don't want to offend him. Therefore, Nathan arranges for Rachel to pretend to be engaged to Eeben Axelroot, a corrupt pilot who lives in the village.
Brother Fowles, the missionary who preceded the Prices in Kilanga, visits the village one day with his Congolese wife and children. Orleanna and her daughters are struck by how his approach to bringing Christianity to Africa differs from Nathan's: He has a much less restrictive view of scripture and worship and seems to be well-liked throughout the village.
One night the Prices are awakened by hordes of ants swarming through the village and eating everything they can, including plants, animals, and people. Everyone in the village flees to the river to escape the ants. Adah, who is disabled, is upset when her mother chooses to save Ruth May rather than her. On that night, Leah tells Anatole, the schoolteacher — with whom she has been spending a great deal of time — that she loves him.
One Sunday, while Nathan is preaching, Tata Ndu interrupts his sermon to hold a vote to determine whether or not the village will choose Jesus as the village's personal God. Jesus loses. Meanwhile, Anatole has given Leah a bow and she has been learning to hunt. When Tata Ndu decides to have a huge hunt to procure some food, Anatole argues to allow Leah to participate. The chief and elders of the village are against a woman participating in the hunt. They hold a vote, and Leah's cause barely wins. After the vote, someone tries to kill Anatole by putting a poisonous snake in his bed.
The hunt takes place, and afterward Leah gets into an argument with the chief's son regarding who killed an antelope. It is obvious that Leah did, but the chief's son doesn't want to admit that a woman could best him. A fight breaks out in the village over the issue.
That night, the Prices' servant, Nelson, is afraid that someone will try to kill him. Leah and her sisters sprinkle ashes on the ground inside and outside of the chicken house where Nelson usually sleeps to catch anyone who might go in there to do him harm. Nelson sleeps at Anatole's that night. The next morning they go to see if anyone entered the chicken house, and they find a poisonous snake there. As the snake flees, it strikes Ruth May and she dies. The footprints in the ashes show that the witch doctor, who has six toes on one foot, planted the snake.
Orleanna prepares Ruth May for burial, bathing her body and sewing a shroud. She moves the dining table outside and places Ruth May's body on it. The village women and children come and express their mourning by kneeling around the body and shrieking. Rachel, Leah, and Adah are all shocked by what has happened and can only kneel and pray. Orleanna brings out all of the other household furniture and goods and gives them to the village women. It begins to rain and Nathan comes out and baptizes the village children in the rain. The children don't understand what he's doing; they only know that their friend is dead. Encircling her body, they call out "Mother may I?"
Orleanna takes her daughters and leaves Kilanga in the rain without ever looking back. On the way to Bulungu, a town several days from Kilanga, Leah falls ill with malaria. She has to be carried on a pallet to Bulungu. When they reach Bulungu, Orleanna negotiates with Axelroot to fly Rachel out of the Congo. She leaves Leah with Anatole and takes Adah on a fruit truck to the embassy in Leopoldville to fly back to the United States.
Even when Leah is well enough to travel, she decides to stay with Anatole. They marry and have four sons. Anatole is imprisoned twice for supporting revolutionary causes. They eventually move their family to Angola, where they start an agricultural commune. Leah learns from Brother Fowles that after many years of moving from village to village, her father was killed at the hands of angry villagers who blamed him for the deaths of their children in the river.
Rachel first lives in Johannesburg, South Africa, with Axelroot and enjoys the society and comforts there. She later marries twice and inherits a hotel in the French Congo from her second husband. She devotes her time and energy into running the hotel and becomes a successful businesswoman.
Adah goes to college in Atlanta becomes a doctor. While in medical school, a neurologist helps her to recover from her disability and learn to walk without a limp. Later, she goes to work for the CDC, investigating tropical diseases, and becomes well-known for the discoveries she makes about AIDS and the Ebola virus.
Orleanna becomes active in the Civil Rights Movement. She can never shake the guilt she feels over Ruth May's death and feels haunted by Ruth May's spirit. In the end, however, she finds peace when she and Adah return to Africa briefly. As they are shopping in the market with Leah and Rachel, the spirit of Ruth May looks on and tells her mother to forgive herself for Ruth May's death.