Nature's Metropolis, William Cronon's classic contribution to the field of environmental history, shifts the focus of its narrative from the individual to the systemic. In other words, it bucks the most popular form of historical storytelling in favor of a more complicated and impersonal one, with the goal of describing factors in the history of Chicago that had been largely overlooked by other scholarship.

As a consequence of this narrative choice, it can be hard to identify "main" characters in his book. In a retrospective interview on the twenty-fifth anniversary of Nature's Metropolis, Cronon said:

There are almost no people in Nature’s Metropolis. And almost no lived, textured reality of classed, gendered, raced people. They’re just not in there. J.M.D. Burrows with his potatoes going down the Mississippi River is probably the most poignant human being in that entire book.

In the largest sense, the main characters in the book are the city of Chicago itself, and the ecosystems that surround it (nature, in the broadest sense). The city is a central actor in the environmental history of the American West and Midwest, as its industrial and infrastructural appetites transformed natural resources into commodities: it is a vortex at the crossroads of the American frontier. Although there are many businessmen and politicians who facilitated the transformation of Chicago's hinterland as part of the rise of the metropolis (the most influential of whom are bear much responsibility for the course of this history), it is the conglomeration of these interests that make the city into one large character, with its tendrils (canals, railroads) reaching in every direction into the countryside.

In classical narratives of environmental transformation, nature is often depicted as the victim of an antagonistic industry or city. In Cronon's book, he works to complicate this narrative—the city of Chicago and its hinterland are linked, neither protagonist or antagonist but two interrelated characters whose interactions shape the course of history.

The central storyline of this book, the conversion of "first nature" around Chicago into urban ecosystems and free market commodities, can be seen this way. An interplay between the city and the country, with consequences for how we think of these two quintessential and often stereotyped "characters" in American history.