When assessing global water resources with hydrological models, it is essential to know about methodological uncertainties. The values of simulated water balance components may vary due to different spatial and temporal aggregations, reference periods, and applied climate forcings, as well as due to the consideration of human water use, or the lack thereof. We analyzed these variations over the period 1901–2010 by forcing the global hydrological model WaterGAP 2.2 (ISIMIP2a) with five state-of-the-art climate data sets, including a homogenized version of the concatenated WFD/WFDEI data set. Absolute values and temporal variations of global water balance components are strongly affected by the uncertainty in the climate forcing, and no temporal trends of the global water balance components are detected for the four homogeneous climate forcings considered (except for human water abstractions). The calibration of WaterGAP against observed long-term average river discharge <i>Q</i> significantly reduces the impact of climate forcing uncertainty on estimated <i>Q</i> and renewable water resources. For the homogeneous forcings, <i>Q</i> of the calibrated and non-calibrated regions of the globe varies by 1.6 and 18.5 %, respectively, for 1971–2000. On the continental scale, most differences for long-term average precipitation <i>P</i> and <i>Q</i> estimates occur in Africa and, due to snow undercatch of rain gauges, also in the data-rich continents Europe and North America. Variations of <i>Q</i> at the grid-cell scale are large, except in a few grid cells upstream and downstream of calibration stations, with an average variation of 37 and 74 % among the four homogeneous forcings in calibrated and non-calibrated regions, respectively. Considering only the forcings GSWP3 and WFDEI_hom, i.e., excluding the forcing without undercatch correction (PGFv2.1) and the one with a much lower shortwave downward radiation SWD than the others (WFD), <i>Q</i> variations are reduced to 16 and 31 % in calibrated and non-calibrated regions, respectively. These simulation results support the need for extended <i>Q</i> measurements and data sharing for better constraining global water balance assessments. Over the 20th century, the human footprint on natural water resources has become larger. For 11–18% of the global land area, the change of <i>Q</i> between 1941–1970 and 1971–2000 was driven more strongly by change of human water use including dam construction than by change in precipitation, while this was true for only 9–13 % of the land area from 1911–1940 to 1941–1970.