The bulk of the novel takes place in Umuofia, a cluster of nine villages on the lower Niger. Umuofia is a powerful clan, skilled in war and with a great population, with proud traditions and advanced social institutions.
Okonkwo has risen from nothing a high position. Through hard work, he has become a great man among his people. He has taken three wives and his barn is full of yams, the staple crop. He rules his family with an iron fist.
One day, a neighbouring clan commits an offense against Umuofia. To avoid war, the offending clan gives Umuofia one virgin and one young boy. The girl is to become the offended party's new wife. The boy, whose name is Ikemefuna, is to be sacrificed, but not immediately. He lives in Umuofia for three years, and during that time he lives under Okonkwo's roof. He becomes like a part of Okonkwo's family. In particular, Nwoye, Okonkwo's oldest son, loves Ikemefuna like a brother. But eventually the Oracle calls for the boy's death, and a group of men take Ikemefuna away to kill him in the forest. Okonkwo, fearful of being perceived as soft-hearted and weak, participates in the boy's death. He does so despite the advice of the clan elders. Nwoye is spiritually broken by the event.
Okonkwo is shaken as well, but he continues with his drive to become a lord of his clan. He is constantly disappointed by Nwoye, but he has great love for his daughter Ezinma, his child by his second wife Ekwefi. Ekwefi has born ten children, but only Ezinma has survived. She loves the girl fiercely. Ezinma is sickly, and sometimes Ekwefi fears that Ezinma, too, will die. Late one night, the powerful Oracle of Umuofia brings Ezinma with her for a spiritual encounter with the earth goddess. Terrified, Ekwefi follows the Oracle at a distance, fearing harm might come to her child. Okonkwo follows, too.
Later, during a funeral for one of the great men of the clan, Okonkwo's gun explodes, killing a boy. In accordance to Umuofia's law, Okonkwo and his family must be exiled for seven years.
Okonkwo bears the exile bitterly. Central to his beliefs is faith that a man masters his own destiny. But the accident and exile are proof that at times man cannot control his own fate, and Okonkwo is forced to start over again without the strength and energy of his youth. He flees with his family to Mbanto, his mother's homeland. There they are received by his mother's family, who treat them generously. His mother's family is headed by Uchendu, Okonkwo's uncle, a generous and wise old man.
During Okonkwo's exile, the white man comes to both Umuofia and Mbanto. The missionaries arrive first, preaching a religion that seems mad to the Igbo people. They win converts, but generally the converts are men of law rank or outcasts. However, with time, the new religion gains momentum. Nwoye becomes a convert. When Okonkwo learns of Nwoye's conversion, he beats the boy. Nwoye leaves home.
Okonkwo returns to Umuofia to find the clan sadly changed. The church has won some converts, some of whom are fanatical and disrespectful of clan custom. Worse, the white man's government has come to Umuofia. The clan is no longer free to judge its own; a District Commissioner judges cases in ignorance. He is backed by armed power.
During a religious gathering, a convert unmasks one of the clan spirits. The offense is grave, and in response the clan decides that the church will no longer be allowed in Umuofia. They tear the building down. Soon afterward, the District Commissioner asks the leaders of the clan, Okonkwo among them, to come see him for a peaceful meeting. The leaders arrive, and are quickly seized. In prison, they are humiliated and beaten, and they are held until the clan pays a heavy fine.
After a release of the men, the clan calls a meeting to decide whether they will fight or try to live peacefully with the whites. Okonkwo wants war. During the meeting, court messengers come to order the men to break up their gathering. The clan meetings are the heart of Umuofia's government; all decisions are reached democratically, and an interference with this institution means the end of the last vestiges of Umuofia's independence. Enraged, Okonkwo kills the court messenger. The other court messengers escape, and because the other people of his clan did not seize them, Okonkwo knows that his people will not choose war. His act of resistance will not be followed by others. Embittered and grieving for the destruction of his people's independence, and fearing the humiliation of dying under white law, Okonkwo returns home and hangs himself.