Objectives Multimorbidity is associated with mortality in high-income countries. Our objective was to investigate the relationship between multimorbidity (≥2 of the following chronic medical conditions: hypertension, diabetes, dyslipidaemia, anaemia, HIV, angina, depression, post-traumatic stress disorder, alcohol dependence) and all-cause mortality in an older, rural black South African population. We further investigated the relationship between HIV multimorbidity (HIV as part of the multimorbidity cluster) and mortality, while testing for the effect of frailty in all models.Design Population cohort study.Setting Agincourt subdistrict of Mpumalanga province, South Africa.Participants 4455 individuals (54.7?male), aged ≥40 years (median age 61 years, IQR 52–71) and resident in the study area.Primary and secondary outcome measures The primary outcome measure was time to death and the secondary outcome measure was likelihood of death within 2 years of the initial study visit. Mortality was determined during annual population surveillance updates.Results 3157 individuals (70.9%) had multimorbidity; 29% of these had HIV. In models adjusted for age and sociodemographic factors, multimorbidity was associated with greater risk of death (women: HR 1.72; 95% CI: 1.18 to 2.50; men: HR 1.46; 95% CI: 1.09 to 1.95) and greater odds of dying within 2 years (women: OR 2.34; 95% CI: 1.32 to 4.16; men: OR 1.51; 95% CI: 1.02 to 2.24). HIV multimorbidity was associated with increased risk of death compared with non-HIV multimorbidity in men (HR 1.93; 95% CI: 1.05 to 3.54), but was not statistically significant in women (HR 1.85; 95% CI: 0.85 to 4.04); when detectable, HIV viral loads were higher in men (p=0.021). Further adjustment for frailty slightly attenuated the associations between multimorbidity and mortality risk (women: HR 1.55; 95% CI: 1.06 to 2.26; men: HR 1.36; 95% CI: 1.01 to 1.82), but slightly increased associations between HIV multimorbidity and mortality risk.Conclusions Multimorbidity is associated with mortality in this older black South African population. Health systems which currently focus on HIV should be reorganised to optimise identification and management of other prevalent chronic diseases.Data are available in a public, open access repository. Data are available upon reasonable request. The HAALSI baseline data are publicly available at the Harvard Centre for Population and Development Studies (HCPDS) programme website [www.haalsi.org]. Data are also accessible through the Inter-university Consortium for Political and Social Research (ICPSR) at the University of Michigan [www.icpsr.umich.edu] and the INDEPTH Data Repository [http://www.indepth-ishare.org/index.php/catalog/113]. Mortality data are available upon request.