Wells along two regional flow paths were sampled to characterize changes in water quality and the vulnerability to contamination of the Memphis aquifer across a range of hydrologic and land-use conditions in the southeastern United States. The flow paths begin in the aquifer outcrop area and end at public supply wells in the confined parts of the aquifer at Memphis, Tennessee. Age-date tracer (e.g. SF₆, ³H, ¹⁴C) data indicate that a component of young water is present in the aquifer at most locations along both flow paths, which is consistent with previous studies at Memphis that documented leakage of shallow water into the Memphis aquifer locally where the overlying confining unit is thin or absent. Mixtures of young and old water were most prevalent where long-term pumping for public supply has lowered groundwater levels and induced downward movement of young water. The occurrence of nitrate, chloride and synthetic organic compounds was correlated to the fraction of young water along the flow paths. Oxic conditions persisted for 10 km or more down dip of the confining unit, and the presence of young water in confined parts of the aquifer suggest that contaminants such as nitrate-N have the potential for transport. Long-term monitoring data for one of the flow-path wells screened in the confined part of the aquifer suggest that the vulnerability of the aquifer as indicated by the fraction of young water is increasing over time.