This dissertation examines the significance of the grotesque to literary naturalism’s engagement with the scientific discourse of the late 19th and early 20th century. The grotesque is a set of artistic principles surrounding the representation of bodies and organic matter that focuses on asymmetry, excess, and ambiguity. Naturalism is a literary movement aimed at transcending the limits of traditional realism by exploring sordid or sensationalist topics and the themes of alienation and determinism through the lens of post-Darwinian psychology, biology, sociology, and criminology. Naturalist texts are preoccupied with the types of knowledge that one can access through fiction. By utilizing the grotesque, naturalist writers are able to produce a form of creatural realism centered on bodies and sensuous experience; this experiential mode of knowledge is placed in productive tension with the culturally-dominant positivist scientific form of knowledge that provide the backbone of naturalist stories. This ‘mixed epistemology’ at the heart of literary naturalism reveals political anxieties surrounding the coherence of social space in the midst of an urbanizing, increasingly diverse American landscape. As a response to this ‘crisis of legibility,’ literary naturalists experiment with two distinct poles of the grotesque—a negative grotesque grounded in alienation, abjection, and fear of degeneration, and a positive grotesque that celebrates disorganized mass life. The chapters of this dissertation contextualize texts from Stephen Crane, Frank Norris, Charlotte Perkins Gilman, and Charles Chesnutt within this cultural moment. Focusing on the grotesque within literary naturalism illuminates the complex epistemological negotiations taking place within each text and the interrelatedness of naturalism’s aesthetics with 19th and early 20th century biopolitics.