Throughout his life, W.E.B. Du Bois actively engaged the scientific racism infecting natural sciences and popular thought. Nevertheless, he also demonstrated a sophisticated and critical engagement with natural science. He recognized that the sciences were socially situated, but also that they addressed real questions and issues. Debate remains, however, regarding exactly how and why Du Bois incorporated such natural scientific knowledge into his own thinking. In this article, we draw on archival research and Du Bois’ own scholarship to investigate his general approach to interdisciplinarity. We address how and why he fused natural scientific knowledge and the influence of physical environs into his social science, intertwining each with his broader intellectual and political aims. This investigation will offer a fuller understanding of the scope and aims of his empirical scholarship. At the same time, it will illuminate a sociological approach to natural science that can still inform scholarship today.