In this paper, two approaches to assess the impacts of climate change on streamflows have been used. In the first approach (direct), a statistical downscaling technique was utilized to predict future streamflows based on large-scale data of general circulation models (GCMs). In the second approach (indirect), GCM outputs were downscaled to produce local climate conditions which were then used as inputs to a hydrological simulation model. In this article, some data-mining methods such as model-tree, multivariate adaptive regression splines and group method of data handling were utilized for direct downscaling of streamflows. Projections of HadCM3 model for A2 and B2 SRES scenarios were also used to simulate future climate conditions. These evaluations were done over three sub-basins of Karkheh River basin in southwest Iran. To achieve a comprehensive assessment, a global uncertainty assessment method was used to evaluate the results of the models. The results indicated that despite simplifications included in the direct downscaling, this approach is accurate enough to be used for assessing climate change impacts on streamflows without computational efforts of hydrological modeling. Furthermore, comparing future climate projections, the uncertainty associated with elimination of hydrological modeling is estimated to be high.