The Lewis & Clark journals contain some of the earliest and detailed written descriptions of a large part of the United States before Euro-American settlement. We used the journal entries to assess the influence of humans on wildlife distribution and abundance. Areas with denser human population, the Columbia Basin and the Pacific Coast, had lower species diversity and abundance of large mammals. The opposite was observed on the Plains. We believe that overhunting before Euro-American contact accentuated by the introduction of the horse may have been major contributors responsible for the historic absence of some species that are present in the archaeological record. The results show the considerable human influence on wildlife under relatively low human population densities. This has major implications for conservation biology and ecological restoration, since human influence is often underestimated when considering the pre-settlement condition.