The opening section of Willa Cather's O Pioneers! is named "The Wild Land." Essentially, this defines one part of the setting--the land which will forever remain wild. Pioneers would go find and settle lands. Even with their settling of the lands, part of the land could never be "tamed." It would always remain out of the control of people. The landscape, described as windblown and covered with hardened sod, is scattered with homes which look as if they are attempting to escape from their own foundations. Refusing to be tamed, the land itself (personified) seems to be just as rugged and knowledgeable as mankind itself.
The windblown Nebraska frontier is the technical setting of the novel. That said, the setting itself seems to be just as much a character as Emil, Alex, and Carl. Its rutted roads metaphorically symbolize the deep wrinkles set into the face of a wise old man or woman. The whipping wind symbolizes the change mankind is always in search of (in regards to mankind's refusing to be tied down).
Perhaps the best illustration of the setting comes in the poem which precedes "The Wild Land." Here, the setting is described as flat and silent, "full of strength and harshness." The poem illustrates mankind's desire to tame the land, yet nature proves to be far more powerful and unmoved, "the eternal, unresponsive sky." The setting, personified and powerful, proves itself to be uncaring about those who try to conquer it. In this section, nature knows it is more powerful and does not let anything root.