The geological setting of an area plays a critical role in the transfer and ultimate distribution of hydrochemical constituents present in groundwater. In southern Ontario, Canada, the present physiography was significantly influenced by glacial processes during the Quaternary period. The heterogeneous nature and complex pattern of shallow subsurface glacial overburden sediments, likely affect the fate of different groundwater constituents. In this study, arsenic (As) and fluoride (F−) concentrations from 515 water wells, that are constructed within overburden sediment, were analyzed with the physiographic map of southern Ontario along with other related variables. Geospatial mapping and several spatial statistical analyses were performed to examine the possible geological influence on As and F− distribution and water-well susceptibility at a regional scale. Key findings suggest four physiographic settings were significant variables influencing the distribution of As and F− in differently constructed bored/dug and drilled wells. Bored/dug wells in Bevelled Till Plains and bored/dug wells in Undrumlinized and Bevelled Till Plains were found to be relatively susceptible to As and F− contamination respectively. In contrast, bored/dug and drilled wells in Drumlinized Till Plains and Drumlins and drilled wells in Sand Plains seemed to be relatively safe from F− and As respectively. The statistical regression analyses suggested that other variables, such as the application of phosphate fertilizer and the textures of till, influenced the spatial distribution of As and F− as well as which types of wells (bored/dug or drilled) were impacted. The geospatial mapping and statistical cluster analysis indicated that the possible sources of elevated As and F− in drilled wells are the clasts of underlying bedrock. The relationship between physiographic settings and impacted overburden wells in southern Ontario provides planners with an approach to water-well susceptibility assessments at the regional scale, which in turn can guide further local analysis for water resource management.