The novel opens on a blustery January day in the fictional town of Hanover, Nebraska, some time between 1883 and 1890. A young woman named Alexandra Bergson has come to the small town to consult a doctor about her dying father. In town, her younger brother Emil's cat gets stuck atop a telegraph pole, and Carl Linstrum, a skinny, melancholy teenager friendly with Alexandra, climbs the pole to retrieve it. In the town drug store, a cute and flirtatious girl named Marie is the toast of the local gentry. Together, the Bergsons and Carl drive their wagon out to their neighboring farms in the vast, dark, savage prairie country around Hanover known as the Divide.
At home, Alexandra speaks with her father John Bergson, who is lying on his deathbed. Bergson immigrated from Sweden, and has spent years battling the land to pay off a mortgage and scratch out a farm. Now, he resolves to leave his land under the care of his wise and resolute oldest child, Alexandra, as his sons, Oscar and Lou, are uninspired, and his wife, while stereotypically industrious, is rather dull. Before he dies, John gives his children practical advice for running the farm and places on Alexandra's shoulders the responsibility for her brothers.
Six months after John Bergson's death, the Bergson children, together with Carl Linstrum, make an excursion to the nearby cave-home of Crazy Ivar, a local eccentric and horse doctor. Ivar is religious, solitary, and strange; the boys distrust him, but Alexandra listens carefully to his sensitive, humane advice about farming. It becomes clear that Alexandra is the most determined of the Bergson children.
Three years after John Bergson's death, a drought hits the Divide, and many families sell their land and leave. Carl Linstrum moves away with his family, and his departure is difficult for Alexandra, since the two have become best friends and soul mates. The two older Bergson boys, Lou and Oscar, suggest that they, too, should sell the farm and leave the Divide. Alexandra disagrees, but determines to find out whether there is, in fact, a better alternative to farming the Divide. She journeys to the nearby river country, where she explores new methods of farming, and realizes that the river country is no more prosperous than the highlands. She is struck by an epiphany, resolving ecstatically to continue farming on the Divide, convinced that it will yield to her efforts and repay them generously. Alexandra suggests a risky scheme: taking out another mortgage and buying even more land. At first, Lou and Oscar reject her plan, but they eventually give in to her calm resolve.
In its first sentence, the novel establishes the kind of symbolism it will use: "The little town of Hanover was trying not to be blown away," the narration opens, personifying the impersonal by positioning the town to stand for its inhabitants. As the incarnated spirit of the settlers, Hanover struggles to stay anchored in the prairie wind. Much of the novel's opening section, titled "The Wild Land," dedicates itself to a description, and more importantly, to a characterization, of the land, setting personified forces and entities into conflict with each other.
The force of nature is so powerful that it can overwhelm the efforts of settlers. In this newly-settled country, "the record of the plow was insignificant, like the feeble scratches on stone left by prehistoric races, so indeterminate that they may, after all, be only the markings of glaciers, and not a record of human strivings." The mark of man upon the land becomes indistinguishable from the marks of nature's own processes. The dying John Bergson remarks that this is a land hostile to cultivation: "Its Genius was unfriendly to man." Similarly, Carl Linstrum believes that "the land wanted to be let alone, to preserve its own fierce strength, its peculiar, savage kind of beauty, its uninterrupted mournfulness."
Carl's musing seems as much a description of himself as of the Nebraska prairie. The land has its own character, but it also reflects the emotions and personalities of the people who interact with it: the dying John Bergson calls the land "unfriendly to man"; and the melancholy Carl believes that the land "wanted to be left alone." Similarly, when Alexandra becomes upset that Carl is leaving the Divide, she looks out over the prairie and sees a country "empty and mournful." In the light of her epiphany, however, Alexandra sees the land as "beautiful and rich and strong and glorious." By the force of her will, she is able to tame the same spirit of the land that her father considered malevolent, making it "ben[d] lower than it ever bent to a human will before." In conquering the land, she reshapes her perception of it.
Alexandra's revelation at the end of the opening section brings her into a new relation to the land. It is possible to consider this abrupt and dramatic conviction regarding the land's beauty and potential as a somewhat clumsy mechanism to advance the plot. That this revelation lacks explanation, like Marie's final reverie and Emil's musical epiphany later in the novel, points to the fact that O Pioneers! does not delve much into its characters' psyches. Rather, the novel's structure consists of various forces placed in opposition to one another, and its core constitutes an exploration of the struggles between these forces, most notably in the measuring of Alexandra's individual agency against the impersonal historical forces that shaped the West. By focusing on the interplay between spirit and circumstance, O Pioneers! proves itself, to some extent, a romantic novel: characters do not develop according to an interior plan, but rather respond to, and are driven by, forces beyond their control. Only after she is shaped by the inexplicable, ecstatic visions of the prairie does Alexandra resolve to transform the land.