Nutrient temporal and spatial distributions were evaluated, in addition to budgets and fluxes derived from the Land-Ocean Interaction in the Coastal Zone (LOICZ) biogeochemical model, to determine dissolved organic matter and inorganic nutrient distribution, flux, and fate in the Mullica River–Great Bay Estuary. Seasonal cycles were observed for dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) with increasing concentrations from spring to fall and maximum concentrations in summer/early fall. Annually, the estuarine system was a net source of DOC (+5 mol m−2 y−1), DON (+0.08 mol m−2 y−1), and dissolved inorganic phosphorus (DIP, +0.010 mol m−2 y−1), a net sink of dissolved inorganic nitrogen (DIN, −0.28 mol m−2 y−1), and in approximate balance of DOP (0.001 mol m−2 y−1). Overall, the upper estuary and mid-estuary served as net sinks for most nutrients, whereas the lower estuary served as a net source. Annual mean nutrient export from the lower estuary to the nearshore coastal region was +3 mol m−2 y−1 for DOC, +0.08 mol m−2 y−1 for DON and DIN, +0.006 mol m−2 y−1 for DOP, and +0.017 mol m−2 y−1 for DIP. In comparison, annual mean watershed DIN input (0.02 mol m−2 y−1) was approximately two times greater than DON input (0.01 mol m−2 y−1), whereas watershed DOP input (0.24 mmol m−2 y−1) was approximately two times greater than DIP input (0.10 mmol m−2 y−1). The lower estuary may serve as a potentially significant source of nutrients for primary production in the nearshore coastal region. Differences in nitrogen and phosphorus pools between watershed inputs and lower estuary exports suggest that the Mullica River–Great Bay estuarine system serves an important role in the cycling of dissolved nitrogen and phosphorus, ultimately controlling the fraction of organic and inorganic nitrogen and phosphorus delivered to the coastal zone.