Rising chloride concentrations pose critical risks to freshwater stream ecosystems in temperate regions like the Delaware River Basin (DRB), USA, where winter deicer applications (i.e., road salt) are common. Increasing chloride concentrations have been documented in the region, but the extent to which chloride exceeds regulatory benchmarks remains unclear because detection of exceedances requires continuous monitoring of chloride (i.e., hourly or daily). A network of 82 non-tidal continuous specific conductance (SC) monitoring sites, spanning varied land use and geological settings, was established across the DRB to address this research need. First, a cluster analysis was conducted to group sites based on their watershed characteristics. Next, regression models for sites and clusters were developed to predict chloride using SC as a proxy. Finally, daily mean and hourly mean chloride concentration predictions were made for a three-year period (2020–2022) at the 82 study sites and analyzed to determine where and when chloride exceeded federal regulatory benchmarks. Chloride exceedance events occurred at 35% of the sites, all of which had 5% impervious cover or greater. Seasonally elevated chloride also was predicted at sites with less than 5% impervious cover. Variability in chloride patterns likely was influenced by deicer material types, winter weather patterns, geological settings, and gaps in data coverage. This study demonstrated the value of SC as a proxy for predicting chloride concentrations and showed how SC-chloride regression relationships vary across settings. More broadly, this study highlighted the value of continuous water quality monitoring to assess effects of freshwater salinization at a regional scale.