Riverine ecosystems are linked to their watersheds, and both land use and physiographic environmental conditions influence nutrient dynamics and water quality. We assessed aquatic nutrients and their relationship with land use and physiographic conditions at multiple spatial scales in the Brazos River watershed (Texas, USA) to examine the interactions between land use and physiography and their combined influences on riverine nutrient dynamics. Patterns in physiography and land use were highly correlated, but physiographic gradients explained ∼2× more of the variability in riverine nutrient concentrations than land use (25 and 12%, respectively). The response of nutrient concentrations to spatial patterns of land use and physiography depended on the specific nutrient and scale of analysis. However, elevated dissolved nutrient concentrations typically were associated with areas of higher rainfall, greater stream density, and more intensive human alteration of the catchment. In contrast, particulate nutrients were more responsive to catchment area and seasonality. Seasonality and reach-scale % rangeland had the strongest independent effects on concentrations of particulate nutrients, whereas the specific ecoregion type and catchment-scale % urban use had the strongest independent effects on dissolved nutrients. Our study highlights the importance of incorporating physiographic environmental gradients when studying the interactions between a river and its watershed, especially in large, complex watersheds or those that cross steep environmental gradients.