The Abay / Upper Blue Nile basin contributes the largest share of discharge to the river Nile. However, the basin exhibits large spatio-temporal variability in rainfall and runoff. Moreover, human activities also impact hydrological processes through intensive agriculture, overgrazing and deforestation, which substantially affect the basin hydrology. Thus, understanding hydrological processes and hydro-climatic variables at various spatio-temporal scales is essential for sustainable management of water resources in the region. This research investigates the hydrology of the basin in depth using a range of methods at various spatio-temporal scales. The methods include long-term trend analysis of hydroclimatic variables, hydrologic responses analysis of land cover change, stable isotope techniques and process based rainfallrunoff modelling. A combination of field investigations with new measurements of precipitation, water levels and stable isotopes as well as existing hydro-climatic data offered gaining new insights about runoff generation processes in headwater catchments. The use of rainfall-runoff modelling in two meso-scale catchments of the Abay basin depict that a single model structure in a lumped way for the entire Abay basin cannot represent all the dominant hydrological processes. The results of the different approaches demonstrated the potential of the methods to better understand the basin hydrology in a data scarce region.