The natural aging process of Chesapeake Bay and its tributary estuaries has been accelerated by human activities around the shoreline and within the watershed, increasing sediment and nutrient loads delivered to the bay. Riverine nutrients cause algal growth in the bay leading to reductions in light penetration with consequent declines in sea grass growth, smothering of bottom-dwelling organisms, and decreases in bottom-water dissolved oxygen as algal blooms decay. Historically, bay waters were filtered by oysters, but declines in oyster populations from overfishing and disease have led to higher concentrations of fine-sediment particles and phytoplankton in the water column. Assessments of water and biological resource quality in Chesapeake Bay and tributaries, such as the Potomac River, show a continual degraded state. In this paper, we pay tribute to Owen Bricker’s comprehensive, holistic scientific perspective using an approach that examines the connection between watershed and estuary. We evaluated nitrogen inputs from Potomac River headwaters, nutrient-related conditions within the estuary, and considered the use of shellfish aquaculture as an in-the-water nutrient management measure. Data from headwaters, nontidal, and estuarine portions of the Potomac River watershed and estuary were analyzed to examine the contribution from different parts of the watershed to total nitrogen loads to the estuary. An eutrophication model was applied to these data to evaluate eutrophication status and changes since the early 1990s and for comparison to regional and national conditions. A farm-scale aquaculture model was applied and results scaled to the estuary to determine the potential for shellfish (oyster) aquaculture to mediate eutrophication impacts. Results showed that (1) the contribution to nitrogen loads from headwater streams is small (about 2 %) of total inputs to the Potomac River Estuary; (2) eutrophic conditions in the Potomac River Estuary have improved in the upper estuary since the early 1990s, but have worsened in the lower estuary. The overall system-wide eutrophication impact is high, despite a decrease in nitrogen loads from the upper basin and declining surface water nitrate nitrogen concentrations over that period; (3) eutrophic conditions in the Potomac River Estuary are representative of Chesapeake Bay region and other US estuaries; moderate to high levels of nutrient-related degradation occur in about 65 % of US estuaries, particularly river-dominated low-flow systems such as the Potomac River Estuary; and (4) shellfish (oyster) aquaculture could remove eutrophication impacts directly from the estuary through harvest but should be considered a complement—not a substitute—for land-based measures. The total nitrogen load could be removed if 40 % of the Potomac River Estuary bottom was in shellfish cultivation; a combination of aquaculture and restoration of oyster reefs may provide larger benefits.