Jim Burden was born in Virginia but comes to Nebraska to live with his grandparents after his parents die. He grows to love the prairie, the adventures and freedom it offers, as well as the stories of his immigrant neighbors. His childhood friendship with Ántonia, a daughter of Bohemian immigrants, is one that will wax and wane as he ages but will remain important throughout his life. Jim matures from a rebellious, moody teen who prefers the company of hired girls to those of his own class, to a serious student and lawyer. Although he enjoys something of a fling with Lena, he feels an enduring, platonic love for Ántonia. Years later he returns to Nebraska to find that his connection to Ántonia and his past are immutable.
Ántonia Shimerda comes to Nebraska with her parents from their native country of Bohemia. She is a warm, vivacious, healthy girl who strikes up an instant friendship with her neighbor Jim, quickly learning all the English can he teach her. She is especially close to her gentle, artistic father, and even after his death she feels his presence. Ántonia works hard to help provide for her family, both in the fields and later as a hired girl in town. Her generous, loving heart turns out to be her downfall when she is tricked out of her money and reputation by a man she loves. Resilient, Ántonia has the child and keeps working. Her value is later recognized by a fellow Bohemian immigrant, and through hard work she and her husband create a bountiful family and farm. Ántonia never forgets her friend Jim, passing on stories of their adventures to her many children.
Lena Lingard grows up destitute, herding cows and wearing rags. Her beauty defies poverty and earns her little but trouble until she has the opportunity to train as a dressmaker. Lena takes the chance to escape her past and learn to make her own living. She vows to never marry. Lena becomes a successful dressmaker and business owner. She shares her affection as she pleases, and she reluctantly sees Jim move on from their relationship, knowing she wouldn't have married him anyway. Lena goes on to have a popular dressmaking business in California.