The book's narrator, Jim Burden, arrives in the fictional town of Black Hawk, Nebraska, on the same train as the Shimerdas. His parents have died so he is going to live with his grandparents. Jim develops strong feelings for Ántonia, something between a crush and a filial bond, and the reader views Ántonia's life, including its attendant struggles and triumphs, through that lens.
The novel is divided into five books, some of which incorporate short stories Cather had previously written, based on her own life growing up on the Nebraska prairies. The volumes correspond roughly to the stages of Ántonia's life, up through her marriage and motherhood, although the third volume, "Lena Lingard," focuses more on Jim's time in college and his affair with Lena, another childhood friend of his, who is also Ántonia's friend.