Regime shifts of major salinity constituents (Ca, Mg, Na, K, SO4, Cl, HCO3, and NO3) in the lower Salinas River, an agricultural ecosystem, can have major impacts on ecosystem services central to continued agricultural production in the region. Regime shifts are large, persistent, and often abrupt changes in the structure and dynamics of social-ecological systems that occur when there is a reorganization of the dominant feedbacks in the system. Monitoring information on changes in the system state, controlling variables, and feedbacks is a crucial contributor to applying sustainability and ecosystem resilience at an operational level. To better understand the factors driving salinization of the lower Salinas River on the central coast of California, we examined a 27-year record of concentrations of major salinity constituents in the river. Although limited in providing an understanding of solute flux behavior during storm events, long-term “grab sampling” datasets with accompanying stream discharges can be used to estimate the actual history of concentrations and fluxes. We developed new concentration–discharge relationships to evaluate the dynamics of chemical weathering, hydrological processes, and agricultural practices in the watershed. Examinations of long-term records of surface water and groundwater salinity are required to provide both understanding and perspective towards managing salinity in arid and semi-arid regions while also enabling determination of the influence of external climatic variability and internal drivers in the system. We found that rock weathering is the main source of Ca, Mg, Na, HCO3, and SO4 in the river that further enables ion exchange between Ca, Mg, and Na. River concentrations of K, NO3, and Cl were associated with human activities while agricultural practices were the major source of K and NO3. A more direct anthropogenic positive trend in NO3 that has persisted since the mid-1990s is associated with the lag or memory effects of field cropping and use of flood irrigation. Event to inter-year scale patterns in the lower Salinas River salinity are further controlled by antecedent hydrologic conditions. This study underscores the importance of obtaining long-term monitoring records towards understanding watershed changes-of-state and time constants on the range of driving processes.