When he is only ten years old, Jim Burden finds himself an orphaned boy in Virginia during the late 1880s. He is forced to move to Nebraska to live with his grandparents and boards a train to their farm with a worker named Jake. On the same train he encounters a bohemian family, the Shimerdas who are found to be buying the land right next to the one belonging to the Burdens. The 13-year old Antonia, who is the closest to his age instantly intrigues Jim Burden.
On his arrival, he is greeted by an Austrian cowboy called Otto Fuchs, who takes him to his grandparents. On the prairie, Jim feels at home with his grandparents who are homely and generous. He also makes friends with the two farmhands, Jake and Otto. He also learns more about his neighbors, who had bought their plot from the only other Bohemian in the area, a Peter Kraijek who had charged them more than the usual price for the land. The Burdens and Shimerdas befriend each other and the children enjoy their little adventures in the outdoors, including Antonia who is also interested in learning English from Jim as well as taking in the American lifestyle. Her parents are more wary about switching over to more leisurely surroundings, especially Mrs. Shimerda who presents the lack of resources at hand and Mr. Shimerda who is homesick, moreover feeing incapable of running a farm by himself. There are four children, two sons and two daughters; the older son is named Ambrosch who is shown to be rude and crass while the younger son is mentally handicapped. Antonia is the eldest daughter and her sister, Yulka, is described as being a pretty and affectionate girl.
Although the Burdens attempt to make the transition for the Shimerdas as hospitable as possible, all is not well in the Bohemian household. The homesick Mr. Shimerda’s high point of the day is when he meets his friends, Pavel and Peter, who are Russian and converse in a language similar to the mother tongue of the Shimerdas. However, just before the first winter of the novel Pavel dies and after losing his friend, Peter moves away to a job in railway construction. Thus, Mr. Shimerda falls further into depression and loses his sprit to work even more. That winter he and his family do not have the money to buy warm clothes or present each other with gifts on Christmas since the snow traps them in from going to the store. They resort to making the gifts themselves and an attempt on the part of the Burdens to assist their neighbors in their time of need is perceived wrongly. They invite the Shimerdas to their home but Mr. Shimerda is aloof and distant while his wife is humiliated and feels that the Burdens treat her family as a charity case.
Just days before Jim’s eleventh birthday and amidst the biggest snowstorm to hit Nebraska since his birth, Mr. Shimerda commits suicide in the barn by shooting himself with a pistol. Although Jake reveals his suspicions about the situation and believes that Mr. Shimerda was murdered, he has no way of proving it so there are no further inquiries about the death. The next day, Jim is alone in the house and senses the spirit of the deceased Mr. Shimerda who glides by him on his way to his beloved homeland, the only place he had ever felt peace.
The family wants the body to be buried in a corner of their land, a place that is being built to be a crossroad for the lane. A fellow Bohemian, Anton Jelinek, helps them in digging the grave and a funeral is arranged for Mr. Shimerda although as Jim observes, the ceremony is arranged in a very careless manner and did not prove to be very memorable.
Winter gone, spring arrives and the children prepare to go to school. However, Antonia decides not to, rather choosing to work in the fields along with her older brother, the de facto breadwinner of the family now that their father is dead. Although they remain friends, Jim becomes busy with schoolwork and loses touch with Antonia who has to stay at the farm. Initially, he resents the time she spends at work and moreover, the Burdens have a tiff with Ambrosch whose rude behavior has escalated even more since last winter. However, the neighbors soon reconcile and all is well again.
When Jim turns 13, the Burdens shift to the town so that it is easier for him to attend school. He fears that this may be the end of his friendship with Antonia but the Burdens’ new neighbor the Harlings take her in as a housekeeper and they see more of each other than they had in years. During those days, working in households as nannies and the help was a common job for immigrant girls and they were termed as the ‘hired girls’ in the town, Black Hawk. Although she spends time with her friend Jim, Antonia forms a kinship with these girls who tend to go dancing at weekends at the local pavilion. However, due to her incessant outgoings, people start to talk about her and the Harlings ask her to stop going at these dances. Antonia quits and starts working for Wick Cutter, who has a notorious reputation in Black Hawk. Now that she no longer stays with the Harlings she has fewer restrictions. She even takes Jim at some these dances and he takes this to mean that Antonia has feelings for him. But when he proposes to her, she dismisses this and states that he is only a little brother to her.
Wick Cutter makes a pass at Antonia and she quits again, this time taking up a job at the only hotel in town. Meanwhile, Jim prepares to pass the admission test for college as his high school graduation soon arrives. Before he leaves for college, he spends one last day with Antonia at the prairie as they both remember the days that have gone by. Although they are amicable to each other, they both understand that it is time for them to part for the time being.
At Lincoln College, he befriends his Latin teacher, Gaston Cleric and renews his friendship with one of the hired girls, Antonia’s friend Lena who starts to visit him regularly at college after they meet when she gets a job in town at a hair salon. They begin dating although Jim is aware of the fact that she has other admirers and he himself is still in love with Antonia. When Gaston decides to move to Harvard, he transfers as well, shifting to Boston to attend school there, biding farewell to Lena.
After finishing school at Harvard, he visits his grandparents at Black Hawk before he starts law school. He enquires after Antonia who, he is surprised to learn, is the unmarried mother of a child. She was to marry the father of her child after she got pregnant, but he ran off before the wedding. She had to move back to the farm where she still works to support her child. Jim goes to see her and again reveals his devotion to her. Antonia is glad to see him, but does not reciprocate his feelings.
Jim promises to keep in touch, but the next time they meet, twenty years have passed. After finishing law school, Jim marries and moves to New York to practice law. When he visits the prairie again, he finds Antonia married to a fellow Bohemian, Anton Cuzak, and is the mother of several children. She still resides at the same farm and at first, she is unable to recognize Jim after so many years, but is elated to see him when she finally does. She gives him a tour of the farm and he is reminded of his past when he sees the children playing around the vegetation and trees.
He stays with them and the next day, he meets Antonia’s husband Anton, who had been away from home. Jim observes the couple and appreciates Anton, who seems to treat his wife with love and respect. He understands the sense of equality and affection between the two and is relieved to hear Anton state to Jim his love for Antonia. Jim stays with Antonia and her family for another day and leaves after that to Black Hawk for a day. He promises to go hunting with her sons before he leaves, but the reader is left wondering about whether Jim aver keeps his promise to visit again.
At Black Hawk, Jim returns to where he stayed in town with grandparents. He visits a dirt path down the farm and imagines himself to have finally reached a full circle of his life by coming back to the start of his journey of life. He is content now, relieved that at least he and Antonia have a past with memories to cherish forever.