Karst aquifers occur in a range of climatic and geologic settings. Nonetheless, they are commonly characterized by their vulnerability to water-quality impairment. Two karst aquifers, the Edwards aquifer in south-central Texas and the Upper Floridan aquifer in western Florida, were investigated to assess factors that control the movement of contaminants to public-supply wells (PSWs). The geochemistry of samples from a selected PSW or wellfield in each aquifer was compared with that from nearby monitoring wells and regional PSWs. Geochemistry results were integrated with age tracers, flow modeling, and depth-dependent data to refine aquifer conceptual models and to identify factors that affect contaminant movement to PSWs. The oxic Edwards aquifer is vertically well mixed at the selected PSW/wellfield, although regionally the aquifer is geochemically variable downdip. The mostly anoxic Upper Floridan aquifer is affected by denitrification and also is geochemically variable with depth. In spite of considerable differences in geology and hydrogeology, the two aquifers are similarly vulnerable to anthropogenic contamination. Vulnerability in studied PSWs in both aquifers is strongly influenced by rapid karst flowpaths and the dominance of young (<10 years) groundwater. Vulnerability was demonstrated by the frequent detection of similar constituents of concern in both aquifers (nitrate, atrazine, deethylatrazine, tetrachloroethene, and chloroform). Specific consideration of water-quality protection efforts, well construction and placement, and aquifer response times to land-use changes and contaminant loading are discussed, with implications for karst groundwater management.