Urban estuaries are subject to frequent stressors, including nutrient loading and hydrological flashiness, which worsen water quality and disrupt ecosystem function. Land use changes associated with urbanization, as well as atypical precipitation conditions can exacerbate stress on estuarine health. However, generalizable patterns and parameters involved in estuarine responses to urbanization and extreme precipitation events remain unknown. We investigated physicochemical factors and urban land-use characteristics that associate with estuarine resistance to precipitation within and across estuaries ranging in urbanization, salinity, and precipitation. Using population and land use/land cover data combined with long-term meteorological, nutrient, and water quality data from the National Estuarine Research Reserve System, we focused on five estuaries distributed across the continental United States. We hypothesized that estuaries with higher urban impact exhibit lower resistance to precipitation events. We investigate this through relationships between the resistance index – a proxy for ecosystem stability calculated using dissolved oxygen – and various physicochemical factors and urban land-use characteristics on local and continental scales. Contrary to our hypothesis, we found that estuaries with higher urban influences were more resistant to precipitation events, and that water temperature, water column depth, nitrogen, and chlorophyll-a were related to estuarine resistance on a continental scale. However, these trends interacted with estuarine salinity and varied across individual estuaries; where we found additional relationships of resistance with salinity, turbidity, phosphate concentrations, N:P ratio, and tree cover. Considering emerging stressors from new climatic scenarios and urbanization-driven changes, these results are important for informing decisions for determining the appropriate estuarine water-quality standards.