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The aim of this article is to determine how human interventions in upstream countries coupled with drought events are affecting the flow regime of downstream countries using the Nile River basin for illustrative purposes. This has been addressed by assessing climate change in the study area through analyses of precipitation data obtained from the Global Precipitation Climatology Centre (GPCC) and detecting if there is a trend, and subsequently calculating drought events in the main basins impacting on the downstream flow. Then river discharge data were analysed using different hydraulic indices at key stations in the downstream country and measuring the alterations occurring in the flow. The degree of alteration is a function of the number of civil engineering projects being in operation and classified by time windows; pre-alteration is between 1900 and 1925, while the alteration period is between 1933 and 2012. The alteration period was classified into three periods based on the degree of alteration. The findings revealed that there are changes in the river flow regime caused by both changes in the rainfall pattern in addition to the regulation in the upstream countries. There is a direct relationship between the interventions in the upstream countries and changes in the flow regime especially when coupled with drought events. By increasing the water usage upstream, there is an increase in the alteration of the flow downstream. The years between 2000 and 2012 were linked to the highest alterations between the modified years.