Despite being globally pervasive, racism, xenophobia, and discrimination are not universally recognised determinants of health. We challenge widespread beliefs related to the inevitability of increased mortality and morbidity associated with particular ethnicities and minoritised groups. In refuting that racial categories have a genetic basis and acknowledging that socioeconomic factors offer incomplete explanations in understanding these health disparities, we examine the pathways by which discrimination based on caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour affect health. Discrimination based on these categories, although having many unique historical and cultural contexts, operates in the same way, with overlapping pathways and health effects. We synthesise how such discrimination affects health systems, spatial determination, and communities, and how these processes manifest at the individual level, across the life course, and intergenerationally. We explore how individuals respond to and internalise these complex mechanisms psychologically, behaviourally, and physiologically. The evidence shows that racism, xenophobia, and discrimination affect a range of health outcomes across all ages around the world, and remain embedded within the universal challenges we face, from COVID-19 to the climate emergency.