Despite some improvement in lowering HIV incidence, HIV-related challenges, such as intimate partner violence (IPV), remain unacceptably high among women in South Africa. For decades, researchers and activists have pointed to the complex and intertwined reality of the substance abuse, violence and AIDS (SAVA) syndemic that endangers women. However, more recent systematic review/meta-analysis evidence points to inconclusive association between IPV and alcohol use. Furthermore, much of the evidence is often non-population-based that focuses on the co-occurrence rather than synergistic SAVA interaction. In this study, using the latest data from the South Africa Demographic and Health Survey (SA-DHS), we identified geographic synergistic clustering of IPV associated with HIV and substance abuse in South Africa as a measure of population-level interactions among these factors. The SA-DHS is a nationally representative sample that includes wide-ranging data on health, social challenges and household geo-locations of 5,874 women who participated in the domestic violence module. First, geographical IPV, harmful alcohol use (as the substance abuse measure available in SA-DHS) and HIV clusters were identified using the Kulldorff spatial scan statistic in SaTScan. Second, synergistic interactions related to recent IPV (i.e. recent physical, sexual, emotional violence during the last 12 months) with harmful alcohol use and HIV challenge were measured using RERI [Relative excess risk due to interaction], AP [attributable proportion] and S [Synergy index]. In our results, we spatially identified geographical physical IPV syndemic interactions in parts of the Eastern Cape/Free State Provinces (RERI = 4.42 [95% CI: 2.34-6.51], AP = 0.56 [95% CI: 0.44-0.68], S = 2.77 [95% CI: 2.01-3.84], but not in other forms of IPV. Although IPV, based on decade old concept of SAVA syndemic, was less common/widespread than expected from the national scale population-based data, we identified population-level physical violence syndemic occurring in South Africa. Our study highlights the need to prioritize public health response targeting vulnerable populations residing in these high-risk areas of syndemic mechanisms linking these synergistic epidemics that women face in South Africa.