O Pioneers! opens on a blustery winter day, in the town of Hanover, Nebraska, sometime between 1883 and 1890. The narrator introduces four principal characters: the very young Emil Bergson; his stalwart older sister, Alexandra; her gloomy friend Carl Linstrum; and a pretty little Bohemian child, Marie Shabata. From town, Emil and Alexandra and their neighbor Carl return home to the desolate stretch of plains known as the Divide. Alexandra's father, John Bergson, is dying. He tells his two eldest sons, Oscar and Lou, that he is entrusting the farmland, and the preservation of all that he has accomplished since his immigration from Sweden, to his daughter.
It becomes clear that Alexandra is stronger and more resolute than her brothers. When drought and depression strike three years later, Alexandra's determination allows her to persevere. Many families, including Carl Linstrum's, sell their farms and move away. But Alexandra believes in the promise of the untamed country, and so she convinces her brothers to re-mortgage their farm and buy more land. She also convinces them to adopt innovative farming techniques.
The narrative jumps sixteen years into the future, when Alexandra's faith in the land has been repaid. Lou and Oscar are married, and each owns his own farm. Alexandra's farm is the most prosperous on the Divide. Emil has been provided the wealth and luxury to leave the Divide for the State University. Crazy Ivar, the elderly, slightly imbalanced man who, earlier in the novel, gave Alexandra some controversial farming advice, now works in Alexandra's stables, although Lou and Oscar disapprove of his presence. Amid this underlying tension, Carl Linstrum returns for a long visit after years of travel. /PARAGRAPH. Meanwhile, Marie Shabata is trapped in an unhappy marriage with a sullen and difficult husband, and it becomes clear that she and Emil are falling in love. Emil decides to travel to Mexico City, fleeing the temptation that Marie presents. Alexandra and Carl slowly regain their teenage intimacy. In reaction, Lou and Oscar drive Carl out of town, fearing that his relationship with Alexandra might threaten their own children's prospects of inheriting Alexandra's farm.
Emil returns from Mexico nearly a year later, only to find that his love for Marie has grown during their separation. Once again, he resolves to flee the Divide. Before he can leave, though, tragedy strikes: his best friend, Amedee, dies unexpectedly. At a church mass, Emil enters a state of rapture and resolves to say farewell to Marie. He finds her in a similar ecstasy in her orchard, and he lies down next to her. Her jealous husband, Frank Shabata, finds them. Blinded by fury, he shoots them both dead.
Months after the murders, Alexandra Bergson has achieved some limited recovery from her sorrow; she now possesses a stoic exhaustion with life. She resolves to try to win a pardon for Frank, who is serving a ten-year sentence in a Lincoln jail. Returning from a visit to Frank in Lincoln, she finds Carl Linstrum waiting for her. As soon as he heard of Emil's death, he returned from Alaska. They find comfort and companionship in each other, and they decide to marry.