In this study, we integrated satellite-drived precipitation and modeled evapotranspiration data (2000–2012) to describe spatial variability of hydrologic sources and sinks in the Nile Basin. Over 2000–2012 period, 4 out of 11 countries (Ethiopia, Tanzania, Kenya, and Uganda) in the Nile Basin showed a positive water balance while three downstream countries (South Sudan, Sudan, and Egypt) showed a negative balance. Gravity Recovery and Climate Experiment (GRACE) mass deviation in storage data analysis showed that at annual timescales, the Nile Basin storage change is substantial while over longer time periods, it is minimal (<1% of basin precipitation). We also used long-term gridded runoff and river discharge data (1869–1984) to understand the discrepancy in the observed and expected flow along the Nile River. The top three countries that contribute most to the flow are Ethiopia, Tanzania, and Kenya. The study revealed that ∼85% of the runoff generated in the equatorial region is lost in an interstation basin that includes the Sudd wetlands in South Sudan; this proportion is higher than the literature reported loss of 50% at the Sudd wetlands alone. The loss in runoff and flow volume at different sections of the river tend to be more than what can be explained by evaporation losses, suggesting a potential recharge to deeper aquifers that are not connected to the Nile channel systems. On the other hand, we also found that the expected average annual Nile flow at Aswan is greater (97 km³) than the reported amount (84 km³). Due to the large variations of the reported Nile flow at different locations and time periods, the study results indicate the need for increased hydrometeorological instrumentation of the basin. The study also helped improve our understanding of the spatial dynamics of water sources and sinks in the Nile Basin and identified emerging hydrologic questions that require further attention.