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Reverand Nathan Price brought his woefully unprepared family to a small village in the former Belgian Congo to do missionary work in 1959. The people speak Kikongo, a language where a word has multiple meanings, depending on its intonation. When the Reverand Price thunders, "Tata Jesus is bangala", meaning "precious", his intonation changes the word into "the poisonwood tree", a poisonous plant that causes skin eruptions. That is just one of many mistakes this arrogant preacher makes in The Poisonwood Bible. He is also clueless about why the villagers refuse to have their children baptized by immersion in a river full of crocodiles.

The story is told through narrations by his wife, Orleanna, and their four daughters. Orleanna helps us understand the source of Nathan's problems, their history back in Georgia, and the role of mothers in the Congo. The oldest daughter is Rachel, a self-absorbed, materialistic teen, whose malapropisms are a source of amusement. The youngest is Ruth May who befriends the village children, but who is in the most danger from diseases and other threats. In the middle are the twins, Leah and Adah. Leah is the social conscience of the novel. Adah limps and very rarely speaks, but writes her feelings in her diary. She has an intelligent, sarcastic wit, and often records events in palindromic phrases.

The author lived in the Belgian Congo as a child, and has woven political and cultural problems into the story. Colonial governments were paternalistic, and worked the Africans in rubber plantations and mines as indentured laborers. After the Congo declared independence, foreign governments played a part in the assassination of the Congo's elected leader. Barbara Kingsolver was a great storyteller, while also showing social injustice, cultural divisions, and religious differences in the Congo.