The water resource of the Blue Nile River in north Africa is under increasing pressure due to rapid population growth and economic development. The situation is aggravated by a lack of coordinated management and governance, partly caused by incomplete knowledge of the water supplies, uses and needs. Proper water management is particularly important now, considering the recently completed and planned mega dams on the Blue Nile River network. This paper reports on the construction of a one-dimensional hydrodynamic model covering the entire Blue Nile River system, from Lake Tana to the confluence with the White Nile, with the aim of quantifying water availability throughout the year, for different conditions. The work included an extensive field measurement campaign along the Blue River and its tributaries, both in Ethiopia and Sudan. Calibrated and validated with independent datasets, the model was used to quantify water uses in the period 2008–2010, which were then compared with the official figures. The results show that the dry season is characterised by extra water losses that should be taken into account when quantifying water needs, especially during the filling up phase of new reservoirs.