This study investigates the coupling of physical and biological processes in the Northern Adriatic Sea through use of a dynamic mass balance approach derived from an interdisciplinary model of hydrodynamics and water quality. Emphasis is placed on modelling the role of nutrient inputs from the Po River and the response of phytoplankton concentrations and distributions, and basin-wide nutrient fluxes. The effects of riverine inflows, seasonal stratification and meteorological forcing were assessed with a dynamically coupled 3D hydrodynamic (ELCOM) and ecological (CAEDYM) model after validation with in situ field and remote sensing data. Model simulation results and mass balance calculations indicate a close coupling of physical and biological processes over a range of space and time scales. Comparison of fluxes from advection and particulate organic matter sedimentation indicate that nutrient and phytoplankton levels of the Northern Adriatic Sea are sensitive to variations in riverine nutrient loadings. A net total phosphorus accumulation of 4.61 × 10 kg⁶ was determined for the basin in 2002, with different climate scenarios and riverine nutrient loadings resulting in varied system responses reflected in this net TP accumulation. Changes in net accumulation of nutrients are considerably lower than variations in nutrient loadings, which suggests that the Northern Adriatic has substantial buffering capacity.