BACKGROUND: International organs such as, the African Union and the South African Government view maternal health as a dominant health prerogative. Even though most countries are making progress, maternal mortality in South Africa (SA) significantly increased between 1990 and 2015, and prevented the country from achieving Millennium Development Goal 5. Elucidating the space-time patterns and risk factors of maternal mortality in a rural South African population could help target limited resources and policy guidelines to high-risk areas for the greatest impact, as more generalized interventions are costly and often less effective. METHODS: Population-based mortality data from 2000 to 2014 for women aged 15-49 years from the Africa Centre Demographic Information System located in the Umkhanyakude district of KwaZulu-Natal Province, South Africa were analysed. Our outcome was classified into two definitions: Maternal mortality; the death of a woman while pregnant or within 42 days of cessation of pregnancy, regardless of the duration and site of the pregnancy, from any cause related to or exacerbated by the pregnancy or its management but not from unexpected or incidental causes; and 'Mother death'; death of a mother whilst child is less than 5 years of age. Both the Kulldorff and Tango spatial scan statistics for regular and irregular shaped cluster detection respectively were used to identify clusters of maternal mortality events in both space and time. RESULTS: The overall maternal mortality ratio was 650 per 100,000 live births, and 1204 mothers died while their child was less than or equal to 5 years of age, of a mortality rate of 370 per 100,000 children. Maternal mortality declined over the study period from approximately 600 per 100,000 live births in 2000 to 400 per 100,000 live births in 2014. There was no strong evidence of spatial clustering for maternal mortality in this rural population. However, the study identified a significant spatial cluster of mother deaths in childhood (p = 0.022) in a peri-urban community near the national road. Based on our multivariable logistic regression model, HIV positive status (Adjusted odds ratio [aOR] = 2.5, CI 95%: [1.5-4.2]; primary education or less (aOR = 1.97, CI 95%: [1.04-3.74]) and parity (aOR = 1.42, CI 95%: [1.24-1.63]) were significant predictors of maternal mortality. CONCLUSIONS: There has been an overall decrease in maternal and mother death between 2000 and 2014. The identification of a clear cluster of mother deaths shows the possibility of targeting intervention programs in vulnerable communities, as population-wide interventions may be ineffective and too costly to implement.