There is growing concern worldwide about the exposure of groundwater resources to pharmaceutically active compounds (PhACs) and agricultural contaminants, such as pesticides, nitrate, and Escherichia coli. For regions with a low population density and an abundance of water, regional contamination assessments are not carried out systematically due to the typically low concentrations and high costs of analyses. The objectives of this study were to evaluate regional-scale contaminant distributions in untreated groundwater in a rural region of Quebec (Canada). The geological and hydrogeological settings of this region are typical of post-glacial regions around the world, where groundwater flow can be complex due to heterogeneous geological conditions. A new spatially distributed Anthropogenic Footprint Index (AFI), based on land use data, was developed to assess surface pollution risks. The Hydrogeochemical Vulnerability Index (HVI) was computed to estimate aquifer vulnerability. Nine wells had detectable concentrations of one to four of the 13 tested PhACs, with a maximum concentration of 116ng·L for benzafibrate. A total of 34 of the 47 tested pesticides were detected in concentrations equal to or greater than the detection limit, with a maximum total pesticide concentration of 692ng·L. Nitrate concentrations exceeded 1mg·L N-NO in 15.3% of the wells, and the Canadian drinking water standard was exceeded in one well. Overall, 13.5% of the samples had detectable E. coli. Including regional-scale sources of pollutants to the assessment of aquifer vulnerability with the AFI did not lead to the identification of contaminated wells, due to the short groundwater flow paths between recharge and the sampled wells. Given the occurrence of contaminants, the public health concerns stemming from these new data on regional-scale PhAC and pesticide concentrations, and the local flow conditions observed in post-glacial terrains, there is a clear need to investigate the sources and behaviours of local-scale pollutants.