Salinity, selenium, and uranium pose water‐quality challenges for the Arkansas River in southeastern Colorado and other rivers that support irrigation in semiarid regions. This study used 31 years of continuous discharge and specific conductance (SC) monitoring data to assess interannual patterns in water quality using mass balance on a 120‐km reach of river. Discrete sampling data were used to link the SC records to salinity, selenium, and uranium. Several important patterns emerged. Consumptive use reduced discharge by a median value of 33% and drove corresponding increases in salinity and uranium concentrations. Increased water availability for irrigation from rainfall and upstream snowpack in 1995–1999 flushed additional salinity and uranium into the river in 1996–2000; average annual total dissolved solids (salinity) concentrations increased 25%, and loads increased 131%. Smaller flushing events have occurred, sometimes lagging an increase in water availability by about one year. The pattern indicates flushing of salts temporarily stored, evaporatively concentrated, or of geologic origin. Mobilization of selenium from the reach was minor compared to salinity and uranium, and net selenium removal from the river was suggested in some years. Several processes related to irrigation could be removing selenium. The results provide context for efforts to improve water quality in the Arkansas River and rivers in other semiarid regions.

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