<p>This paper uses the Budyko method to investigate mean annual streamflow changes, due to climate variation and human influence, in the important Karkheh River Basin in western Iran. To validate the results, hydrological modelling (HBV model) and Landsat 5 Thematic Mapper (TM) images were used for the study period between 1980 and 2012. The recently developed DBEST (Detecting Breakpoints and Estimating Segments in Trend) method identified an abrupt negative change in the streamflow trend in 1994–5. The results show that the observed streamflow decrease in the Karkheh River is associated with both climate variation and human influence. The combination of increased irrigated area (from 9 to 19 % of the total basin area), reduction of forests (from 11 to 3 %), and decreasing annual precipitation has significantly reduced streamflow in the basin. Moreover, the results show that the streamflow reduction in the Karkheh Basin is more sensitive to the change in precipitation than temperature.</p>