What became the modern city of Chicago began as a settlement at a particularly felicitous location, where a river emptied into one of the Great Lakes. Not only were the plains around the river well suited to agriculture, the adjacent areas were excellent grazing lands. The indigenous peoples before European contact primarily engaged in hunting and gathering, but they had established trade relations with other groups throughout the Midwest. Primarily tracing the changes that occurred after Europeans were well established in eastern North America, Cronon shows how the colonial trade patterns—mainly established by French explorers and merchants—paved the way for US post-independence expansion.

Beyond the natural advantages (or “first nature”), it was the intensive human intervention and manipulation of the landscape (or “second nature”) that supported what became the city’s meteoric rise. With each phase of intensification—canals that joined rivers and lakes, trails for riders and wagons, and especially the railroads—the city experienced another growth spurt. Having a viable hub greatly facilitated the further development of the Midwest, and the connection with the Mississippi on the western side of Illinois cemented the North-South axis that connected not only the northern United States but also Canada to the Gulf of Mexico. Rather than poised at the edge of a frontier, as Frederick Turner had posited, Chicago emerges as centrally located conceptually as well as physically.

There was a steep price to pay, however, for this ascent, with the accompanying Euro-American homesteading, urbanization, and ultimately industrialization. In the spirit of the commercial drive to maximize investment on capital, especially in the post-Civil War years, Chicago provided an array of services that were increasingly crucial to not just the region but the nation; these included physical plants such as for food processing, along with banking and related financial services. At the same time, Native American people were killed and their lands destroyed, and those who remained were pushed to the edges of the Plains states, accomplished by military campaigns and the creation of the reservation system. Rapid urban growth and industrialization, largely unhindered by regulation, also created irreversible ecological disasters whose legacy remains to this day.

Cronon argues that Chicago opened the Great Plains to settlement by "second nature," the "improvement" of natural resources available. Because of it's location and the effort and capital invested in the enterprise, Chicago become a hub through which settlement flowed. It provided markets for agricultural goods and timber, transportation infrastructure in the form of railroads, processing plants for meats, and credit markets through which capital flowed. The crucial point is that this is, to say the least, not necessarily a positive development. Chicago both provided a template for and a base for the ecological annihilation of the Great Plains. It also was the space in which the commodification of living things, especially livestock, became a reality. Eventually, the people who moved onto the plains perceived Chicago as a place where parasitical bankers and magnates grew rich at their expense. Cronon argues that without the city, the frontier would not have been possible, a inversion of Frederick Jackson Turner's "frontier thesis." City and country were tied together inextricably.