Estuaries integrate atmospheric, watershed, oceanic, and human influences over space and time. Therefore, spatial and temporal patterns in estuarine water-column properties are useful as metrics to evaluate external factors related to internal processes. The National Estuarine Research Reserve monitoring program, including the North Inlet–Winyah Bay complex in South Carolina, provides an ideal setting to track water quality relationships. Our goal was to assess hydrography, chlorophyll a, and particulate and dissolved materials from monitoring data collected at sites from both the salt and estuarine marsh components since 1993–94. Salinity, turbidity, dissolved organic carbon, suspended solids, and chlorophyll a were much greater at the estuarine site, whereas organic nitrogen dominated the total nitrogen pool at both locations. Nitrate was a significant fraction of the total nitrogen pool at the estuarine site but not within the salt marsh. Whereas dissolved organic nitrogen was positively correlated to water temperature, nitrate concentrations were the lowest in the summer. Principal components analysis identified seasonal patterns within the salt marsh for temperature, chlorophyll a, ammonium, suspended solids, and particulate nitrogen. These parameters, grouped together as a primary component, were positively correlated to Spartina alterniflora biomass. In contrast, the estuarine site was more characterized by salinity, pH, and dissolved organic carbon. Although the water-column properties of the salt marsh site reflected a high degree of internal production and remineralization in the summer, patterns at the estuarine site were more likely influenced by seasonal changes in circulation and biogeochemical processing common to coastal plain estuaries.