Anthropogenic nutrient enrichment from wastewater treatment plants (WWTPs) drives water quality in estuaries globally, but the ecological impacts of effluent nutrient reductions from WWTP upgrades are uncertain, especially in hydrologically complex estuaries. In California’s Sacramento-San Joaquin Delta (Delta), a major WWTP upgrade was completed in 2021 that reduced effluent ammonium and increased effluent nitrate concentrations, with an overall reduction in dissolved inorganic nitrogen. Some researchers predicted this change would bolster the pelagic food web by fostering a more abundant and nutritious phytoplankton community; however, the ecosystem response was uncertain. We evaluated the spatial extent of the WWTP effluent influence on nutrient concentrations across the Delta before and after the upgrade and assessed the phytoplankton response. We analyzed water quality data from 22 Delta sites over the four years preceding and three years following the upgrade. Generalized additive models showed that, prior to the upgrade, effluent nutrient (i.e., ammonium, nitrate, dissolved inorganic nitrogen, and phosphate) inputs affected Delta nutrient concentrations up to approximately 80 kilometers downstream. Following the upgrade, effluent ammonium concentrations declined to non-detectable levels. Furthermore, effluent dissolved inorganic nitrogen and phosphate affected Delta site concentrations in a smaller spatial area post-upgrade. Finally, we found that ammonium and nitrate concentrations downstream of the WWTP were primarily positively associated with chlorophyll concentration and the prevalence of diatoms. These initial findings suggest that WWTP upgrades can alter nutrient regimes in complex estuaries with implications for primary producers.