Epistemologies of the Unknowable in Nineteenth-century U.S. Literature is an interdisciplinary analysis of an emergent nineteenth-century cultural concern about the limits of knowledge, a shadow discourse lurking behind the growing confidence in positivism. My central claim is that a range of U.S. authors began asking epistemological questions about the limits of what can be known by any one person, or all persons collectively. These authors anticipated what we call “standpoint particularity:” the premise that we can only inhabit each limited point of view because of our embodied being. They also explored whether whatever lies beyond those limits—what I am calling the unknowable—might be a problem, or a resource, or both. By reflecting on the value of the unknowable, authors created a new vocabulary for understanding the place of “humanity.” Combining textual analysis with intellectual history and archival studies, I show that investigations into the unknowable helped literary writers, especially those excluded from the period’s knowledge-making due to their race and gender, invent their epistemological discourse to scrutinize the areas outside existing frameworks of recognition. The frameworks such as empiricism and religion seemed to be malfunctioning or irredeemably harmful. Their literary epistemologies were an invitation to and demand for reconsidering the established and popular ways of thinking about knowledge, race, and humanity. I move from the interpersonal mysteries in Herman Melville’s 1850s fiction, through the instances of unknowability within enslavement in Black autobiographies between the 1840s and 1890s, and in Sui Sin Far’s proto-sociological sketches of Chinatowns at the turn of the century. I also examine formalistic affordances of literary genres through which these inquiries are dramatized: the short story, detective fiction, Gothic modes, and aphorism. Taken together, these literary writings rebut Alexis de Tocqueville’s assertion that Americans in the nineteenth-century “denied […] the limits of understanding.” By examining the question of what sits outside our knowledge-making capacities, this dissertation proposes that we can recover how the period’s literary aesthetics attempted to create a more complete vision of the strange and elusive scope of the human experience.