HIV-induced stigma and discrimination remain a prevalent global challenge especially in low-income countries which may compromise the emotional and social well-being of people living with HIV (PLHIV). Despite the efforts so far, the incidence of HIV-related stigma remains high in Ghana. Drawing on the Goffman’s theory of social stigma and interpretivist research paradigm, the paper explores the lived experiences of 123 PLHIV in HIV-endemic cities in Ghana. Findings suggest that PLHIV largely suffer from three levels of stigma—internal, received and associated—with complex discriminatory dimensions. PLHIV are stigmatised and discriminated against at home, in the community and in institutional settings. This is manifested through familial neglect, social exclusion and poor access to jobs and health services. These prejudices presaged suicidal ideations, non-disclosure of HIV serostatus, poor adherence to treatment interventions and further spread of the epidemic. Progressive social and health policy framework and programmes on eradicating HIV are pressing. These should conspicuously include HIV-related stigma and discrimination through behavioural change and culturally acceptable public education about the myths and realities surrounding HIV in order to mitigate the associated debilitating outcomes.