Evidence suggests that Indigenous Peoples have the highest rate of death by homicide compared to other ethnic groups in the USA. Despite this alarming disparity and its fatal implications, there seems little attention paid to this crisis outside of Indigenous communities, and literature on the violence perpetrated against this population is comparatively scarce. Among the 574 federally recognized tribes and 326 reservations across the USA, there is great diversity. Yet, Indigenous Peoples share similar experiences of colonialism, genocide, oppression, and marginalization. These experiences highlight how existing social structures and systems continue to function as oppressive forces against Indigenous Peoples. The current study meta-analytically synthesized the existing body of knowledge to summarize current understandings of the relative risk of homicide faced by Indigenous Peoples. Following systematic searches of published and gray literature, data were extracted from 38 eligible studies. As hypothesized, Indigenous Peoples’ risk of homicide was consistently about three times greater than that of others in the USA over the past generation, but counter-hypothetically no gender divide was observed. These findings suggest prevalent, grave and longstanding social-structural and ultimately, health inequities among Indigenous Peoples in the USA. Future research needs and policy implications are discussed.