Freshwater Salinization Syndrome (FSS) refers to the interactive effects of salt ions on the degradation of the natural, built, and social systems. FSS can mobilize chemical mixtures, termed ‘chemical cocktails’, in watersheds. The formation of chemical cocktails across space and time depends on the amounts and types of salt pollution, the surrounding land use including conservation and restoration areas, and the location along the flowpath in the watershed. We investigated (1) the formation of chemical cocktails temporally and spatially and (2) the natural capacity of watersheds and streams to attenuate salt ions along flowpaths with conservation and restoration efforts. We monitored high-frequency temporal and longitudinal spatial chemical changes in stream water in response to different pollution events (i.e., road salt, stormwater runoff, wastewater effluent, and baseflow conditions) and several types of watershed management efforts (i.e., national parks, regional parks, and floodplain reconnection) in six urban watersheds in the Chesapeake Bay region. There were significant relationships between watershed impervious surface cover and mean concentrations of salt ions (Ca2+, K+, Mg2+), metals (Fe, Mn, Sr2+), and nutrients (total dissolved nitrogen) (p < 0.05). Principal component analysis (PCA) indicates that chemical cocktails which formed along flowpaths in response to winter road salt applications were enriched in salts and metals (e.g., Na+, Mn, and Cu). During most baseflow and stormflow conditions, chemical cocktails that were less enriched in salt ions and trace metals were attenuated downstream. There was also downstream attenuation of FSS ions during baseflow conditions through management efforts including a regional park, national park, and floodplain restoration. Conversely, chemical cocktails that formed in response to multiple road salt applications or prolonged road salt exposure did not show patterns of attenuation downstream. The spatial patterns were quite variable, with increasing, plateauing, or decreasing patterns based on the magnitude, timing, duration of road salt loading, and extent of management efforts. Our results suggest that FSS can mobilize multiple contaminants along watershed flowpaths, however, the capacity of current watershed management strategies such as restoration and conservation areas to attenuate FSS is limited.