The Poisonwood Bible is divided up into seven parts, each of which is told in short chapters from the perspective of one of the women in the Price household.
In "Genesis," the family first arrives in the Congo, leaving their friends and family back in Georgia. They are unprepared for the trip, though they attempt to bring large amounts of their possessions with them. They soon find that even these possessions do them little good in the African jungle. They are forced to quickly learn the ways of the jungle, both in the manner in which Reverend Price tries to preach to the people, and in the ways their native Georgia plants won't flower in the African jungle and are washed away when the heavy rains finally come.
In "The Revelation," the political situation of the Congo becomes clearer. Specifically, there are threats that the communists from Russia will come in and take over, as well as rumblings of a new leader named Patrice Lumumba emerging from the people. The Prices also begin to learn some of the language and customs of the village, though there are new revelations each day that prevent them from fully assimilating into the culture.
"The Judges" focuses on the Price's struggles to stay in the Congo as the political and living situations deteriorate. Lumumba is elected President of the Congo, and with him comes the danger of war from those that oppose him. The missionary society that supports the Price's pulls their stipend and suggests that they leave, though Nathan Price refuses. Ruth May and Orleanna both take to bed, sick and depressed, and it is up to the three older daughters to provide for the family. The situation reaches a climax as a horde of ants invades the village, leaving a wake of destruction.
"The Bel and the Serpent" is the climax of the book. The family discovers that Ruth May has stopped taking her quinine pills to fight off malaria, and she just barely escapes a fatal illness. The political situation in the village, moreover, deteriorates when Reverend Price is voted out of the church. Complicating matters, Leah falls in love with Anatole, the local village school teacher, and takes a more authoritative role in the family. Yet, the village witch doctor curses the family when Leah attempts to hunt with the other village men and places a green mamba snake in the Price's chicken house. As the girls attempt to drive the snake out, it bites Ruth May, killing her.
With the death of her youngest daughter, Orleanna flees with her living children, leaving her husband in the village. In this chapter, named "Exodus," they travel on foot through mud and rain, contracting dangerous cases of malaria, until they finally make it to a neighboring village. Rachel makes a deal with a local pilot/mercenary to take her away and they are informally married in South Africa. Leah decides to stay in Africa with Anatole who she soon marries as well. Only Adah and Orleanna make it out of Africa and back to Georgia where they are forced to deal with the memories of Africa on their own terms.
"Song of the Three Children" details the lives of the living daughters as they grow older through the years. Rachel marries and divorces two husbands and is finally widowed after her third husband dies and leaves her a resort hotel to care for in the neighboring French Congo. Though it is not the American life she dreams of, she finds her calling and happiness in the relative wealth of Africa. Leah, on the other hand, decides to live in the abject poverty of Africa. She and Anatole have four children and, after Anatole is imprisoned multiple times, they end up on a communal farm in Angola where they fight for African freedom. Adah dedicates her life to science and becomes a doctor in Atlanta. Eventually she ends up studying viruses in Africa. Orleanna moves to Sanderling Island, Georgia, where she lives in retirement, thinking often of Africa and hoping for forgiveness for the child she lost.
The final section, "The Eyes in the Trees," is told through the omniscient voice of Ruth May as she watches her living sisters and old mother return for one final trip to Africa. They want to put a tombstone on her grave, but soon learn that the village of Kilanga no longer exists. Ruth May offers final forgiveness to her mother and a posthumous reflection on the nature of life and death.