Over the course of the HIV/AIDS epidemic, black Americans have become a central target of US public health prevention efforts. And today, HIV/AIDS is understood to disproportionately affect black Americans. This markedly contrasts with knowledge about the disease and efforts to prevent it in the first decade of the epidemic in the US, when expert and lay understandings and responses centred on white gay males. This article demonstrates that explaining these historical reversals as purely reflective of epidemiological data – or best knowledge available – is insufficient. Drawing on the concept disease regimes and utilising a discursive analysis of epidemiological results and editorial commentary published from 1981 to 1994 in the Morbidity and Mortality Weekly Reports (MMWR), this article argues for a socio‐political explanation for the changing colour of HIV/AIDS. That is, it scrutinises institutional and discursive practices that within the HIV/AIDS prevention field and disease discourse constituted a ‘regime of black American exclusion’ (1981–1992) and a ‘regime of black American inclusion (1993–present day).