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The Adige River Basin (ARB) provides a vital water supply source for varying demands including agriculture (wine production), energy (hydropower) and municipal water supply. Given the importance of this river system, information about past (paleo) drought and pluvial (wet) periods would quantity risk to water managers and planners. Annual streamflow data were obtained for four gauges that were spatially located within the upper ARB. The Old World Drought Atlas (OWDA) provides an annual June–July–August (JJA) self-calibrating Palmer Drought Severity Index (scPDSI) derived from 106 tree-ring chronologies for 5414 grid points across Europe from 0 to 2012 AD. In lieu of tree-ring chronologies, the OWDA dataset was used as a proxy to reconstruct both individual gauge and ARB regional streamflow from 0 to 2012. Principal component analysis (PCA) was applied to the four ARB streamflow gauges to generate one representative vector of regional streamflow. This regional streamflow vector was highly correlated with the four individual gauges, as coefficient of determination (R2) values ranged from 85% to 96%. Prescreening methods included correlating annual streamflow and scPDSI cells (within a 450 km radius) in which significant (p ≤ 0.01 or 99% significance) scPDSI cells were identified. The significant scPDSI cells were then evaluated for temporal stability to ensure practical and reliable reconstructions. Statistically significant and temporally stable scPDSI cells were used as predictors (independent variables) to reconstruct streamflow (predictand or dependent variable) for both individual gauges and at the regional scale. This resulted in highly skillful reconstructions of upper ARB streamflow from 0 to 2012 AD. Multiple drought and pluvial periods were identified in the paleo record that exceed those observed in the recent, historic record. Moreover, this study concurred with streamflow reconstructions in nearby European watersheds.