High variability in precipitation and streamflow in the semiarid northern Great Plains causes large uncertainty in water availability. This uncertainty is compounded by potential effects of future climate change. We examined historical variability in annual and growing season precipitation, temperature, and streamflow within the Little Missouri River Basin and identified differences in the runoff response to precipitation for the period 1976-2012 compared to 1939-1975 (n = 37 years in both cases). Computed mean values for the second half of the record showed little change (<5%) in annual or growing season precipitation, but average annual runoff at the basin outlet decreased by 22%, with 66% of the reduction in flow occurring during the growing season. Our results show a statistically significant (p < 0.10) 27% decrease in the annual runoff response to precipitation (runoff ratio). Surface-water withdrawals for various uses appear to account for <12% of the reduction in average annual flow volume, and we found no published or reported evidence of substantial flow reduction caused by groundwater pumping in this basin. Results of our analysis suggest that increases in monthly average maximum and minimum temperatures, including >1°C increases in January through March, are the dominant driver of the observed decrease in runoff response to precipitation in the Little Missouri River Basin.