Until now, driving mechanisms behind recurring droughts and hydroclimate variations that controls the Nile River Basin (NRB) remains poorly understood. Our results show significant hydroclimatic changes that contributed to recent increasing aridity of NRB since the 1970s. Besides climate warming, the influence of stronger ENSO and Indian Ocean dipole (IOD) in NRB has increased after 1980s, which have significantly contributed to NRB’s drought severity at inter-annual to inter-decadal timescales. Our results demonstrate that warming, El Niño and IOD have played a crucial role on NRB’s inter-decadal hydroclimate variability, but IOD has played a more important role in modulating NRB’s hydroclimate at higher timescales than El Niño. Results also indicate that the impacts of positive phases of ENSO and IOD events are larger than the negative phases in the NRB hydroclimate. Further, the southward (westward) shift in stream functions and meridional (zonal) winds caused an enhancement in the blocking pattern, with strong anticyclonic waves of dry air that keeps moving into NRB, has resulted in drier NRB, given stream function, geopotential height and U-wind anomalies associated with El Niño shows that changes in regional atmospheric circulations during more persistent and stronger El Niño has resulted in drier NRB. After 1970s, El Niño, IOD, and drought indices shows significant anti-phase relationships, which again demonstrates that more frequent and severe El Niño and IOD in recent years has led to more severe droughts in NRB. Our results also demonstrate that IOD and and the western pole of the Indian Ocean Dipole (WIO) are better predictors of the Nile flow than El Niño, where its flow has decreased by 13.7 (upstream) and by 114.1 m3/s/decade (downstream) after 1964. In summary, under the combined impact of warming and stronger IOD and El Niño, future droughts of the NRB will worsen.