Two commonly used approaches for water quality monitoring are probabilistic and targeted. In a probabilistic approach like the US Environmental Protection Agency’s National Rivers and Streams Assessment, monitoring sites are selected using a statistically representative approach. In a targeted approach like that used by many monitoring organizations, monitoring sites are chosen individually to answer specific questions. One important goal of both approaches is documenting long-term changes in water quality. Here, we compare chloride change results in US rivers and streams between the early 2000s and early 2010s from both approaches. The probabilistic approach provided an unbiased representation of change in all US rivers and streams, but was designed to measure low-streamflow conditions within a spring/summer index period during periodic survey years. The targeted approach was focused on larger, more developed watersheds but samples were collected frequently throughout the assessment period in different seasons and streamflows. The probabilistic results showed a small decrease in chloride concentrations in rivers and streams with the lowest concentrations, but no consistent increase or decrease in the remainder. The increased granularity of the targeted results showed that there was, in fact, a mix of changes occurring, with increases at 132 sites, decreases at 112 sites, and relatively stable conditions at 55 sites. The combined results suggest that chloride is not responding to a widespread, common driver across the USA and that management of chloride would be most effective when targeted regionally or locally.