Groundwater contamination from geogenic sources poses challenges to many countries, especially in the developing world. In Tanzania, the elevated fluoride (F^–) concentration and related chronic fluorosis associated with drinking F^– rich water are common in the East African Rift Valley regions. In these regions, F^– concentration is space dependence which poses much uncertainty when targeting safe source for drinking water. To account for the spatial effects, integrated exploratory spatial data analysis, regression analysis, and geographical information systems tools were used to associate the distribution of F^– in groundwater with spatial variability in terrain slopes, volcanic deposits, recharge water/vadose materials contact time, groundwater resource development for irrigated agriculture in the Sanya alluvial plain (SAP) of northern Tanzania. The F^– concentration increased with distance from steep slopes where the high scale of variation was recorded in the gentle sloping and flat grounds within the SAP. The areas covered with debris avalanche deposits in the gentle sloping and flat grounds correlated with the high spatial variability in F^– concentration. Furthermore, the high spatial variability in F^– correlated positively with depth to groundwater in the Sanya flood plain. In contrast, a negative correlation between F^– and borehole depth was observed. The current irrigation practices in the Sanya alluvial plain contribute to the high spatial variability in F^– concentration, particularly within the perched shallow aquifers in the volcanic river valleys. The findings of this study are important to the overall chain of safe water supply process in historically fluorotic regions. They provide new insights into the well-known F^– contamination through the use of modern geospatial methods and technologies. In Tanzania’s context, the findings can improve the current process of drilling permits issuance by the authority and guide the local borehole drillers to be precise in siting safe source for drinking water.