The purpose of this study was to investigate sustainability of water resources management in the Upper Great Ruaha River Catchment (UGRRC) and the impacts of water availability and use dynamics to the downstream river flows. Trend analysis, regime shift analysis, low flow analysis and generation of indicators of hydrologic alteration (IHA) were among the methods used to investigate variability of rainfall and river flows. Water abstraction and use patterns were investigated through intensive hydrometric monitoring and social survey methods. An integrated river basin decision-making framework was developed and used to assess the sustainability of water resources management. The study found out that although river flows entering the UGRRC have not changed much between pre 1980 and post 1980 time windows, split sample analysis of the flows showed that the mean annual runoff exiting the UGRRC decreased from 2537.55 Mm 3 to 2053.77 Mm 3. The dry season flows also decreased by 57% between the two time windows and the decrease, found to be due to human interventions taking place in the plains, is statistically significance at 5% significance level. Analysis of IHA parameters revealed a progressive decline in flows lower than Q 30 . The analysis showed that 1-day minimum flow exiting the UGRRC decreased from 2.572 m 3 /s to 0.1221 m 3 /s; Q 90 decreased from 2.720 m 3 /s to 0.266 m 3 /s; zero flow days have increased from 0.25 days to 22 days per annum in the post-impact period; and the minimum flows now, start two weeks earlier as compared to the pre-impact window. This implies a faster depletion rate of dry season flows in the UGRRC.iii Comprehensive assessment of water demands and water resources of the Mkoji sub- catchment revealed that during the dry season water resources are the limiting production factors as they are not enough to meet the current requirements for irrigation, let alone other water use sectors. The formal water rights were found to be problematic as in eight out of the 12 studied river systems water rights were higher than the actual river flows. However, the granted formal water rights were much higher compared to the actual water requirements resulting into over-abstractions of water above what is needed for crop production. As such streams run dry half way through the sub catchment as water that would have kept them flowing throughout the year are used up for irrigation. The result is that downstream water users suffer more from water shortages and some sub-catchments (e.g. Mkoji) are now closed during the dry season, contributing zero flows to the Great Ruaha River. Assessment of sustainability showed that current water resources management practices in the UGRRC are unsustainable and if maintained, they could lead to severe social, environmental and economic consequences. The study concludes that there is a need to review the formal water rights to conform to current water availability and requirements and to improve monitoring and data management system in order to fulfil the mission, goals and objectives of water resources management in Tanzania. This study has demonstrated the value of combining different research methods and analyses and the role of simple decision support tools to assist in reaching and evaluating decisions concerning sustainable water resources management.