A combination of driving forces are increasing pressure on local, national, and regional water supplies needed for irrigation, energy production, industrial uses, domestic purposes, and the environment. In many parts of Europe groundwater quantity, and in particular quality, have come under sever degradation and water levels have decreased resulting in negative environmental impacts. Rapid improvements in the economy of the eastern European block of countries and uncertainties with regard to freshwater availability create challenges for water managers. At the same time, climate change adds a new level of uncertainty with regard to freshwater supplies. In this research we build and calibrate an integrated hydrological model of Europe using the Soil and Water Assessment Tool (SWAT) program. Different components of water resources are simulated and crop yield and water quality are considered at the Hydrological Response Unit (HRU) level. The water resources are quantified at subbasin level with monthly time intervals. Leaching of nitrate into groundwater is also simulated at a finer spatial level (HRU). The use of large-scale, high-resolution water resources models enables consistent and comprehensive examination of integrated system behavior through physically-based, data-driven simulation. In this article we discuss issues with data availability, calibration of large-scale distributed models, and outline procedures for model calibration and uncertainty analysis. The calibrated model and results provide information support to the European Water Framework Directive and lay the basis for further assessment of the impact of climate change on water availability and quality. The approach and methods developed are general and can be applied to any large region around the world.