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Populations in peri-urban communities of Sub-Saharan Africa frequently depend on shallow aquifers and on-site sanitation facilities concurrently. Routinely, domestic wells end up too close to toilet facilities, risking groundwater contamination. For coastal communities, saltwater intrusion adds to the risk of groundwater contamination. This study assessed both risks in five peri-urban communities of Cape Coast, Ghana. Groundwater samples collected from 40 domestic wells were analyzed for physicochemical and microbial constituents. Multivariate statistics including hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to classify and link contaminants to potential sources. Results indicate high enteric bacteria contamination in 98% of the samples, as well as high enrichment in physicochemical constituents, tied largely to impacts of on-site sanitation facilities. We found that wells located within 25 m of septic tanks/toilet facilities contained higher contaminant loads than those without such facilities within 25 m of their locations. Similarly, for wells located close to point sources, the closer the water table is below the land surface (within 2 m), the higher the contaminant loads. Lastly, using molar ratios of Cl - /HCO 3 - and Na + /Cl - with R-mode HCA, the study isolated a few wells, located within 2 km of the coastline, that are experiencing effects of saltwater intrusion. Overall, this study provides useful information for aiding groundwater quality mitigation policy, and the baseline data for aiding future investigations in the study area. It also has broader policy implications for other peri-urban settings throughout Ghana and the entire Sub-Saharan Africa.