Structural racism is increasingly recognized as a key driver of health inequities and other adverse outcomes. This paper focuses on structural racism as an “upstream” institutionalized process, how it creates health inequities and how structural racism persists in spite of generations of efforts to end it. So far, “downstream” efforts to reduce these health inequities have had little success in eliminating them. Here, we attempt to increase public health awareness of structural racism and its institutionalization and sociopolitical supports so that research and action can address them. This paper presents both a theoretic and an analytic approach to how structural racism contributes to disproportionate rates of HIV/AIDS and related diseases among oppressed populations. We first discuss differences in disease and health outcomes among people who use drugs (PWUD) and other groups at risk for HIV from different racial and ethnic populations. The paper then briefly analyzes the history of racism; how racial oppression, class, gender and other intersectional divisions interact to create health inequities; and how structural racism is institutionalized in ways that contribute to disease disparities among people who use drugs and other people. It examines the processes, institutions and other structures that reinforce structural racism, and how these, combined with processes that normalize racism, serve as barriers to efforts to counter and dismantle the structural racism that Black, indigenous and Latinx people have confronted for centuries. Finally, we discuss the implications of this analysis for public health research and action to undo racism and to enhance the health of populations who have suffered lifetimes of racial/ethnic oppression, with a focus on HIV/AIDS outcomes.