Introduction The rapid ageing of populations around the world is accompanied by increasing prevalence of multimorbidity. This study is one of the first to present the prevalence of multimorbidity that includes HIV in the complex epidemiological setting of South Africa, thus filling a gap in the multimorbidity literature that is dominated by studies in high-income or low-HIV prevalence settings.Methods Out of the full sample of 5059 people aged 40+, we analysed cross-sectional data on 10 conditions from 3889 people enrolled in the Health and Ageing in Africa: A longitudinal study of an INDEPTH Community in South Africa (HAALSI) Programme. Two definitions of multimorbidity were applied: the presence of more than one condition and the presence of conditions from more than one of the following categories: cardiometabolic conditions, mental disorders, HIV and anaemia. We conducted descriptive and regression analyses to assess the relationship between prevalence of multimorbidity and sociodemographic factors. We examined the frequencies of the most prevalent combinations of conditions and assessed relationships between multimorbidity and physical and psychological functioning.Results 69.4 per cent (95% CI 68.0 to 70.9) of the respondents had at least two conditions and 53.9% (52.4–55.5) of the sample had at least two categories of conditions. The most common condition groups and multimorbid profiles were combinations of cardiometabolic conditions, cardiometabolic conditions and depression, HIV and anaemia and combinations of mental disorders. The commonly observed positive relationships between multimorbidity and age and decreasing wealth were not observed in this population, namelydue to different epidemiological profiles in the subgroups, with higher prevalence of HIV and anaemia in the poorer and younger groups, and higher prevalence of cardiometabolic conditions in the richer and older groups. Both physical functioning and well-being negatively associated with multimorbidity.Discussion More coordinated, long-term integrated care management across multiple chronic conditions should be provided in rural South Africa.