To improve quantitative understanding of mixed-land-use impacts on nutrient yields, a nested-scale experimental watershed study design (n = 5) was applied in a 303(d), clean water act impaired urbanizing watershed of the lower Missouri River Basin, USA. From 2010 to 2013, water samples (n = 858 sample days per site) were analysed for total inorganic nitrogen (TIN-N), nitrite (NO2–N) nitrate (NO3–N), ammonia (NH3–N), and total phosphorus (TP-P). Annual, seasonal, and monthly flow-weighted concentrations (FWCs) and nutrient yields were estimated. Mean nutrient concentrations were highest where agricultural land use comprised 58% of the drainage area (NH3 = 0.111 mg/l; NO2 = 0.045 mg/l; NO3 = 0.684 mg/l, TIN = 0.840 mg/l; TP = 0.127 mg/l). Average TP-P increased by 15% with 20% increased urban land use area. Highly variable annual precipitation was observed during the study with highest nutrient yields during 2010 (record setting wet year) and lowest nutrient yields during 2012 (extreme drought year). Annual TIN-N and TP-P yields exceeded 10.3 and 2.04 kg ha−1 yr−1 from the agricultural dominated headwaters. Mean annual NH3–N, NO2–N, NO3–N, TIN-N, and TP-P yields were 0.742, 0.400, 4.24, 5.38, and 0.979 kg ha−1 yr−1, respectively near the watershed outlet. Precipitation accounted for the majority of the explained variance in nutrient yields (R2 values from 0.68 to 0.85). Nutrient yields were also dependent on annual precipitation of the preceding year (R2 values from 0.87 to 0.91) thus enforcing the great complexity of variable mixed-land-use mediated source-sink nutrient yield relationships. Study results better inform land managers and best management practices designed to mitigate nutrient pollution issues in mixed-land-use freshwater ecosystems. Copyright © 2015 John Wiley & Sons, Ltd.