My Ántonia is presented as a manuscript. In a short introduction, an unnamed narrator describes a train journey across Iowa with an old friend, Jim Burden, now a successful railway lawyer in New York. They fall to talking about a Bohemian girl they both knew in childhood, and Jim agrees to write down everything her name recalls to him. The book that follows is his account, titled by his own hand 'My Ántonia.'
Jim's story begins with his arrival in Nebraska as a ten-year-old orphan sent from Virginia to his grandparents' farm. On the same night, the Shimerdas, a Bohemian immigrant family, get off the same train, bound for a wild and unbroken claim nearby. Among them is Ántonia, a quick, warm girl a little older than Jim. The first book follows the children through the seasons of the open country, the kindness and hardship of frontier life, and the slow ruin of the Shimerdas, which ends in Mr. Shimerda's suicide during a brutal winter.
When Jim's grandparents move into the town of Black Hawk, Ántonia and other immigrant daughters come in as hired girls in the houses of the townspeople. Cather draws the small town closely: its respectable families, its narrowness, the dances that the country girls bring to life, and the social line that keeps the hired girls apart. Jim, growing up, admires their energy and resents the town's timidity, but he too is moving away from that world toward university.
The later books carry Jim outward. He studies in Lincoln, drawn to Latin poetry and to Lena Lingard, another of the country girls now making her own way as a dressmaker. He goes east to Harvard and into a career, and for twenty years he loses sight of Ántonia. In the meantime her own story turns hard: she is courted and abandoned by a railroad man, bears his child alone, and goes back to work the land without complaint.
In the final book Jim returns to Nebraska and finds Ántonia married to a Bohemian farmer, surrounded by many children and a thriving fruit farm. She is weathered and aged but full of the same vitality, a woman who has poured her strength into planting, raising, and harvesting. Jim sees in her the meaning of the whole adventure of his childhood, and the book closes on what he calls the precious, incommunicable past that the two of them possess together.