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The assessment of water balance components using global hydrological models is subject to climate forcing uncertainty as well as to an increasing intensity of human water use within the 20th century. The uncertainty of five state-of-the-art climate forcings and the resulting range of cell runoff that is simulated by the global hydrological model WaterGAP is presented. On the global land surface, about 62 % of precipitation evapotranspires, whereas 38 % discharges into oceans and inland sinks. During 1971–2000, evapotranspiration due to human water use amounted to almost 1 % of precipitation, while this anthropogenic water flow increased by a factor of approximately 5 between 1901 and 2010. Deviation of estimated global discharge from the ensemble mean due to climate forcing uncertainty is approximately 4 %. Precipitation uncertainty is the most important reason for the uncertainty of discharge and evapotranspiration, followed by shortwave downward radiation. At continental levels, deviations of water balance components due to uncertain climate forcing are higher, with the highest discharge deviations occurring for river discharge in Africa (−6 to 11 % from the ensemble mean). Uncertain climate forcings also affect the estimation of irrigation water use and thus the estimated human impact of river discharge. The uncertainty range of global irrigation water consumption amounts to approximately 50 % of the global sum of water consumption in the other water use sector.