Toward the end of Man and Nature (1864), George Perkins Marsh wrote about his fear that a sea-level canal across the Isthmus of Darién might divert the Gulf Stream and alter global climate. This article uses Marsh’s surprising digression to illuminate what I call the “Knowledge Anthropocene,” an intellectual enterprise that changed our understandings of earth systems as rapidly as humans were changing the earth. In Marsh’s case, he wrote amidst a rapid acceleration in knowledge about the relationship between geology, geography, ocean currents, and climate that has become critical to our understanding of the global climate system today.