In order to study the change trend of water quality of the Minjiang Estuary and the reasons for it exceeding the seawater quality standard limit, a two-dimensional non-stationary hydrodynamic water quality model was constructed of the Minjiang River covering the downstream to the estuary based on the results of the detailed survey of the sewage outfalls. The main pollutants of CODMn, inorganic nitrogen and reactive phosphate were used as indicators to predict the effects of different hydrological and exogenous pollution loads on the water quality of the Minjiang Estuary, so as to elucidate the spatial and temporal response of water quality to the pollutants. The results show that the response of water quality of the Minjiang Estuary to different hydrology showed significant spatiotemporal variations. CODMn and inorganic nitrogen of the Minjiang Estuary were greatly affected by the upstream water quality, whereas the effect of reactive phosphate was relatively small; under the influence of the tidal currents, the water quality in the high tide period was better than that in the neap tide period, and that in tide rising was better than tide ebbing; when the discharge water quality of the Shuikou Reservoir was set as best in the year or 30% reduction of downstream pollutants, both conditions could not guarantee that the inorganic nitrogen and reactive phosphate concentrations of the estuary would meet the standards. Therefore, it is recommended that more stringent control requirements for total nitrogen and total phosphorus should be enforced on the discharge of the Shuikou Reservoir.