Multiple techniques, including thermal infrared aerial remote sensing, geophysical and geological data, geochemical characterization and radium isotopes, were used to evaluate the role of groundwater as a source of dissolved nutrients, carbon, and trace gases to the Okatee River estuary, South Carolina. Thermal infrared aerial remote sensing surveys illustrated the presence of multiple submarine groundwater discharge sites in Okatee headwaters. Significant relationships were observed between groundwater geochemical constituents and 226Ra activity in groundwater with higher 226Ra activity correlated to higher concentrations of organics, dissolved inorganic carbon, nutrients, and trace gases to the Okatee system. A system-level radium mass balance confirmed a substantial submarine groundwater discharge contribution of these constituents to the Okatee River. Diffusive benthic flux measurements and potential denitrification rate assays tracked the fate of constituents in creek bank sediments. Diffusive benthic fluxes were substantially lower than calculated radium-based submarine groundwater discharge inputs, showing that advection of groundwater-derived nutrients dominated fluxes in the system. While a considerable potential for denitrification in tidal creek bank sediments was noted, in situ denitrification rates were nitrate-limited, making intertidal sediments an inefficient nitrogen sink in this system. Groundwater geochemical data indicated significant differences in groundwater chemical composition and radium activity ratios between the eastern and western sides of the river; these likely arose from the distinct hydrological regimes observed in each area. Groundwater from the western side of the Okatee headwaters was characterized by higher concentrations of dissolved organic and inorganic carbon, dissolved organic nitrogen, inorganic nutrients and reduced metabolites and trace gases, i.e. methane and nitrous oxide, than groundwater from the eastern side. Differences in microbial sulfate reduction, organic matter supply, and/or groundwater residence time likely contributed to this pattern. The contrasting features of the east and west sub-marsh zones highlight the need for multiple techniques for characterization of submarine groundwater discharge sources and the impact of biogeochemical processes on the delivery of nutrients and carbon to coastal areas via submarine groundwater discharge.