Cholera is a global public health problem with ramifications on families, communities and nations. This study examined the spatial clusters of cholera deaths in Mainland Tanzania. A retrospective study design was employed and data about cholera deaths for the years 2015-2018 were collected from the Ministry of Health, Community Development, Gender and Children. We calculated the Local Moran’s index to determine spatial patterns of cholera deaths, followed by spatial scan statistics to detect and map cholera death clusters. Results show that Katavi, Rukwa, Tabora, Iringa, Manyara, Mbeya, Singida and Dodoma are the regions within significant highrisk clusters of cholera deaths in Mainland Tanzania. Dodoma region was the most significant high-risk region to suffer from cholera deaths in all four years studied. The risk of having cholera death in the Dodoma region was 7.88 times higher compared to other regions. We conclude that, the Ministry of Health should pay attention to the factors that make the region the most significant high risk of cholera deaths in the country and measures to control cholera deaths should vary based on the extent of the problem across the regions. This will invariably enable Tanzania to achieve the WHO-led Global Task Force objective of reducing the number of cholera deaths by 90 per cent by 2030.