Beginning in the mid-1990s, the construct of historical trauma was introduced into the clinical and health science literatures to contextualize, describe, and explain disproportionately high rates of psychological distress and health disparities among Indigenous populations. As a conceptual precursor to racial trauma, Indigenous historical trauma (IHT) is distinguished by its emphasis on ancestral adversity that is intergenerationally transmitted in ways that compromise descendent well-being. In this systematic review of the health impacts of IHT, 32 empirical articles were identified that statistically analyzed the relationship between a measure of IHT and a health outcome for Indigenous samples from the United States and Canada. These articles were categorized based on their specific method for operationalizing IHT, yielding 19 articles that were grouped as historical loss studies, 11 articles that were grouped as residential school ancestry studies, and three articles that were grouped as “other” studies. Articles in all three categories included diverse respondents, disparate designs, varied statistical techniques, and a range of health outcomes. Most reported statistically significant associations between higher indicators of IHT and adverse health outcomes. Analyses were so complex, and findings were so specific, that this groundbreaking literature has yet to cohere into a body of knowledge with clear implications for health policy or professional practice. At the conceptual level, it remains unclear whether IHT is best appreciated for its metaphorical or literal functions. Nevertheless, the enthusiasm surrounding IHT as an explanation for contemporary Indigenous health problems renders it imperative to refine the construct to enable more valid research.