The spatio-temporal freshwater river run-off pattern from individual basins, including their run-off magnitude and change (1979/1980-2013/2014), was simulated for the Andes Cordillera west of the Continental Divide in an effort to understand run-off variations and freshwater fluxes to adjacent fjords, Pacific Ocean, and Drake Passage. The modelling tool SnowModel/HydroFlow was applied to simulate river run-off at 3-h intervals to resolve the diurnal cycle and at 4-km horizontal grid increments using atmospheric forcing from NASA Modern-Era Retrospective Analysis for Research and Applications (MERRA) data sets. Simulated river run-off hydrographs were verified against independent observed hydrographs. For the domain, 86% of the simulated run-off originated from rain, 12% from snowmelt, and 2% from ice melt, whereas for Chile, the water-source distribution was 69, 24, and 7%, respectively. Along the Andes Cordillera, the 35-year mean basin outlet-specific run-off (L s(-1) km(-2)) showed a characteristic regional hourglass shape pattern with highest run-off in both Colombia and Ecuador and in Patagonia, and lowest run-off in the Atacama Desert area. An Empirical Orthogonal Function analysis identified correlations between the spatio-temporal pattern of run-off and flux to the El Nino Southern Oscillation Index and to the Pacific Decadal Oscillation.