Apalachicola Bay is a productive estuary located in the northern Gulf of Mexico. The high productivity is, in part, the result of the Apalachicola River delivering freshwater and nutrients to the Bay. Nutrient input supports high levels of phytoplankton productivity, which supports the Bay’s secondary productivity. Diversion of water from headwaters of the Apalachicola River during summer has been proposed to satisfy upstream freshwater requirements for recreation and agriculture. Knowledge of the ecology of phytoplankton and zooplankton in the Bay is needed to help predict the effects of upstream water diversion on Apalachicola Bay. In this study, the temporal and spatial distribution of phytoplankton size composition, growth, biomass, productivity, microzooplankton bacterivory, herbivory, production, and Acartia tonsa herbivory, carnivory, egg production rate, and egg production efficiency were determined in Apalachicola Bay during 2003 and 2004. Phytoplankton growth, biomass, productivity, total ingestion rates and production rates of microzooplankton, and total ingestion rates and egg production rates of Acartia tonsa peaked during summer within lower salinity (<20 psu) waters. Microzooplankton ingested, on average, ten times more phytoplankton productivity than A. tonsa. Compared to the 24 year average river discharge, river discharge into Apalachicola Bay was above average during 2003 and below average during 2004. On average, 100% and about 50% of the surface salinity of the Bay was <20 psu during summer 2003 and summer 2004, respectively. Nutrient concentrations, at a specific salinity, were higher during 2003 than during 2004. Phytoplankton growth and productivity, as well as total ingestion rates and production rates of microzooplankton, at a specific salinity, were higher during summer 2003 than during summer 2004. It is expected that withdrawal of freshwater from the Apalachicola River during summer will lead to reduced higher trophic level production in Apalachicola Bay because of (1) reduced productivity of phyto- and microzooplankton at a specific salinity and (2) increased areal extent of higher salinity water (>20 psu) where phytoplankton growth, biomass, and productivity and zooplankton productivity is low. Implications of these results are also discussed with respect to our understanding of estuarine planktonic food web structure.