In this study stream flow drought was analyzed in Karkheh, Karoon and Dez basins in southwestern Iran. The main aims of this paper are to determine, 1) spatial aspects of stream flow drought, 2) homogenous regions, 3) the effective factors that affect stream flow drought and 4) regional regression models. To attain such aims daily time series of discharges were considered, tested and adjusted in 54 hydrometric stations. Based on truncation level method (at 70% level) the annual maximum series (AMS) drought deficit volume and duration series were extracted. Maps of spatial variation of these indices were showed. Frequency analysis was carried out for mentioned time series. Probability distribution functions including Gamma (Pearson's, type III), Weibull, Logarithmic-normal, Johnson, Double exponential, Generalized Pareto (GP) were used and best models were determined by goodness of fit test. More than 35 important characteristics including physiographic, climatic, geologic, and vegetation cover were considered as influential factors in the regional drought analysis. According to the results of factor analysis, six most effective factors were identified as area, rainfall from December to February, the percent of area with Normalized Difference Vegetation Index (NDVI) of less than 0.1, the percent of convex area, drainage density and the minimum of watershed elevation as a total, these six fact explain more than 90.9% variance. Based on conclusions of factor analysis, homogenous regions were determined by cluster analysis and discriminate function analysis. Suitable multivariate regression models were performed and evaluated for stream flow drought deficit volume with 2, 50, and 100-year return periods. The significance level of regression models was 0.01. The results showed that the watershed area is the most effective factor with high correlation with deficit volume. Drought duration was not a suitable drought index for regional analysis.