In the humid, temperate Delaware River Basin (DRB) where water availability is generally reliable, summer low flows can cause competition between various human and ecological water uses. As temperatures continue to rise, population increases and development expands, it is critical to understand historical low flow variability to anticipate and plan for future flows. Using a sample of 325 U.S. Geological Survey gages, we evaluated spatial patterns in several low flow metrics, the biophysical and climatic drivers of these metrics, and trends in low flows for two periods: 1950-2018 and 1980-2018. We calculated the annual 7-day low flow and date, low flow deficit as the departure below a long-term daily flow threshold and the number of discrete low flow periods below this threshold. We also aggregated several climate metrics to watershed scale and used existing watershed properties quantifying land cover, topography, soils, geology, and human activity. Random forest models were used to assess the hierarchy of variable importance in explaining mean-annual low flow variability for each low flow metric using all gages. We find muted regional patterns in mean-annual low flow and low flow variability, likely due to the myriad of anthropogenic, landscape, and flow modifications that obscure flow regimes from their natural characteristics. In contrast, individual years show markedly different spatial patterns in low flow magnitude and severity. Coincident with increases in precipitation, 7-day low flows have generally increased and low flow deficits decreased for both 1950-2018 and 1980-2018 periods. However, 7-day low flows have decreased in the Coastal Plain physiographic province where water use and impervious area have increased in recent decades, highlighting the effects of land and water management on low flows. With continued change expected in the DRB, additional research needs are highlighted to enable estimation of future low flows and to plan for periods of prolonged low flow.