Hypoxia and anoxia occurred in the upper Delaware Estuary throughout much of the 20th century and diminished over the past several decades. I reviewed 30 yr of data from my laboratory's research efforts, 40 yr of consistent monitoring data from a multistate agency, results from inconsistent data collection from the past century, and anecdotal information to construct a long-time picture of the decline and increase of dissolved oxygen concentrations (DO) in the urban region of the estuary. The primary cause of the DO decline appeared to be inputs or allochthonous materials from urban sources (reduced nitrogen and carbon). In spite of extremely high nutrient concentrations, excess algal production did not influence DO anywhere along the tidal freshwater stretch or the saline portion of the well-mixed Delaware Estuary; and it does not have an influence today. The nutrient loading to the Delaware Estuary is very high, yet the typical signs of eutrophication are not obvious. Based on a model of apparent oxygen utilization, the Delaware Bay apparently had higher primary production 50 yr ago, a time when nutrient concentrations were as high or higher than today, shellfish and finfish production were apparently also higher, and DO was close to saturation. This analysis is offered as guidance in assessing and managing estuarine eutrophication, which is too often considered narrowly to be the result of inadvertent overfertilization by nutrients or a single nutrient element.