Estuaries worldwide are undergoing changes to patterns of aquatic productivity because of human activities that alter flow, impact sediment delivery and thus the light field, and contribute nutrients and contaminants like pesticides and metals. These changes can influence phytoplankton communities, which in turn can alter estuarine food webs. We used multiple approaches-including high-resolution water quality mapping, synoptic sampling, productivity and nitrogen uptake rates, Lagrangian parcel tracking, enclosure experiments and bottle incubations-over a short time period to take a “spatial snapshot” of conditions in the northern region of the San Francisco Estuary (California, USA) to examine how environmental drivers like light availability, nutrients, water residence time, and contaminants affect phytoplankton abundance and community attributes like size distribution, taxonomic structure, and nutrient uptake rates. Zones characterized by longer residence time (15–60 days) had higher chlorophyll-a concentrations (9 ± 4 µg L⁻¹) and were comprised primarily of small phytoplankton cells (<5 µm, 74 ± 8%), lower ammonium concentrations (1 ± 0.8 µM), higher nitrate uptake rates, and higher rates of potential carbon productivity. Conversely, zones characterized by shorter residence time (1–14 days) had higher ammonium concentration (13 ± 5 µM) and lower chlorophyll-a concentration (5 ± 1 µg L⁻¹) with diatoms making up a larger percent contribution. Longer residence time, however, did not result in the accumulation of large (>5 µm) cells considered important to pelagic food webs. Rather, longer residence time zones had a phytoplankton community comprised primarily of small cells, particularly picocyanobacteria that made up 38 ± 17% of the chlorophyll-a – nearly double the concentration seen in shorter residence time zones (22 ± 7% picocyanobacterial of chlorophyll-a). Our results suggest that water residence time in estuaries may have an effect as large or larger than that experimentally demonstrated for light, contaminants, or nutrients.