Water quality in urban streams is critical for the health of aquatic and human life, as it impacts both the environment and water availability. The strong impacts of changing climate and land use on water quality necessitate a better understanding of how stream water quality changes over space and time. To this end, four key water-quality parameters—
Escherichia coli (
E. coli), nitrate (NO
3−), sulfate (SO
42−), and chloride (Cl
−)—were collected at 12 sites along Fall Creek and Pleasant Run streams in Indianapolis, Indiana USA from 2003 to 2021 on a seasonal basis: March, July, and October each year. Two-way ANOVA tests were used to determine the impacts of seasonality and location on these parameters. Correlation and RDA (redundancy analysis) were used to determine the importance of climatic drivers. Linear regressions were used to quantify the impacts of land-use types on water quality integrating buffer zone size and sub-watershed analysis. Strong seasonal variations of the water-quality parameters were found. March had higher levels of NO
3−, SO
42−, and Cl
− than other months. July had the highest
E. coli concentrations compared to March and October. Seven-days antecedent snow and precipitation were found to be significantly related to Cl
− and log
10(
E. coli) and can explain up to 53% and 31% of their variations, respectively. Spatially, urban built-up land in a 1000 m buffer around the sampling sites was positively correlated with the log
10(
E. coli) variation, while lawn cover was positively related to NO
3− concentrations within 500 m buffers. Conversely, NDVI (Normalized Difference Vegetation Index) values were negatively related to all variables. In conclusion,
E. coli is more impacted by higher precipitation and urban land coverage, which could be related to more combined sewer overflow events in July. Cl
− peaking in March and its relationship with snow indicate salt runoff during snow melting events. NO
3− and SO
42− increases are likely due to fertilizer input from residential lawns near streams. This suggests that Indianapolis stream water-quality changes are influenced by both changing climate and land-cover/-muse types.
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