Mathematical models are needed to estimate environmental concentrations of engineered nanoparticles (NPs), which enter the environment upon the use and disposal of consumer goods and other products. We present a spatially resolved environmental fate model for the James River Basin, Virginia, that explores the influence of daily variation in streamflow, sediment transport, and stream loads from point and nonpoint sources on water column and sediment concentrations of zinc oxide (ZnO) and silver (Ag) NPs and their reaction byproducts over 20 simulation years. Spatial and temporal variability in sediment transport rates led to high NP transport such that less than 6% of NP-derived metals were retained in the river and sediments. Chemical transformations entirely eliminated ZnO NPs and doubled Zn mobility in the stream relative to Ag. Agricultural runoff accounted for 23% of total metal stream loads from NPs. Average NP-derived metal concentrations in the sediment varied spatially up to 9 orders of magnitude, highlighting the need for high-resolution models. Overall, our results suggest that "first generation" NP risk models have probably misrepresented NP fate in freshwater rivers due to low model resolutions and the simplification of NP chemistry and sediment transport.