This study utilised data from the National Income Dynamics Study, a longitudinal study with a sample of approximately 28 000 people, to investigate the cross-sectional and spatial distribution of multimorbidity and the association with socioeconomic disadvantage in South Africa for 2008 and 2012. Multimorbidity increased in prevalence from 2.73% to 2.84% in adults between 2008 and 2012 and was associated with age, socioeconomic deprivation, obesity and urban areas. Hypertension was found frequently coexisting with diabetes. Spatial analysis showed clusters (hot spots) of higher multimorbidity prevalence in parts of KwaZulu-Natal and the Eastern Cape, which compared with the socioeconomic disadvantage spatial pattern. Although these results were limited to a district level analysis, this study has provided a platform for future local level research and has provided insight into the socioeconomic determinants of disease multimorbidity within a developing country.