AbstractWe present a comprehensive analysis of water availability under plausible future climate conditions in a heavily irrigated agricultural watershed located in the middle section of the Rio Grande Basin in the United States Desert Southwest. Future managed streamflow scenarios (through year 2099) were selected from among 97 scenarios developed based on downscaled, bias‐corrected global climate model outputs to evaluate future inflows to the principal surface water storage reservoirs, possible future reservoir releases, and groundwater pumping to sustain irrigated agriculture. The streamflow projections describe a wide range of dry and wet conditions compared to the average historical flows in the river, indicating significant uncertainty in future water availability in the Rio Grande Basin. We applied the Soil and Water Assessment Tool to illustrate the impact of climate futures on different components of the water budget at a watershed scale. Results indicate declining reliability of reservoir storage to meet the water demand of irrigated agriculture. The impact of declining surface water can be offset by increasing the pressure on the already‐strained groundwater resources. However, the region should be prepared to use slightly saline (total dissolved solids [TDS] > 1,000 mg/L) and moderately saline groundwater (TDS > 3,000 mg/L) as fresh groundwater in the regional aquifer is depleted within the 21st Century under hotter and drier conditions and status quo agricultural land and water management practices.