Water quality degradation has been a significant concern in the White River watershed of Indiana. As a consequence of long-term inputs of industrial and domestic effluents, and urban and agricultural runoff, the White River has been adversely affected. Some major on-going concerns include excess nutrients, organic compounds, and salinity. Water quality degradation effects extend beyond the local scale, as the White River is a headwater stream and drains into the Mississippi River. Water quality issues become more complex with changing climate, which shifts streamflow regime and water quality. One emerging water quality concern regarding climate change is irrigation suitability of water under the potential shift from rain-fed agriculture to irrigation agriculture in the Midwest. To address these issues, this thesis research: 1) analyzed the long-term secondary water quality data using a novel approach, Weighted Regression on Time, Discharge and Seasons; and 2) collected bi-weekly water samples from the White River during the crop growing season of 2019, and comprehensively analyzed the irrigation suitability of the water. Long-term water quality data analysis of five monitoring sites show that overall flow-normalized concentration and flux of biochemical oxygen demand (BOD) and nitrate-nitrite nitrogen increased from 2002 to 2018. The only exception occurred at the Walnut monitoring site where both nitratenitrite nitrogen concentration and flux decreased. Analysis of pollutant sources indicates that point source pollution and combined sewage outflows may have a substantial contribution to nutrient pollution, and agricultural and urban runoff has a big impact on the both the nutrient and BOD load in the river. Irrigation suitability analysis concludes that the water is mostly suitable for irrigation; however, suitability exhibits distinct patterns between May–July and August–October. An average of 7.8% of samples from May-July are unsuitable for irrigation, while an average of 24.5% of samples from August-October are unsuitable for irrigation. Considering that AugustOctober is the dry and low-flow season when water demand is high, the results suggest a notable possibility that water is unsuitable for irrigation when most needed. This is the first comprehensive study to evaluate irrigation suitability of surface water in the Midwest United States. Meanwhile, the long-term water quality analysis and identification of pollution sources are critical for understanding the driver of water quality in the context of climate and streamflow changes. The results of this study will inform water resources managers responsible for formulating future conservation plans.