African monsoon precipitation experienced a dramatic change in the course of the Holocene. The pace with which the African monsoon shifted from a strong early to middle to a weak late Holocene is critical for our understanding of climate dynamics, hydroclimate-vegetation interaction, and shifts of prehistoric human settlements, yet it is controversially debated. On the basis of planktonic foraminiferal Ba/Ca time series from the eastern Mediterranean Sea, here we present a proxy record of Nile River runoff that provides a spatially integrated measure of changes in East African monsoon (EAM) precipitation. The runoff record indicates a markedly gradual middle to late Holocene EAM transition that lasted over 3500 years. The timing and pace of runoff change parallels those of insolation and vegetation changes over the Nile basin, indicating orbitally forced variation of insolation as the main EAM forcing and the absence of a nonlinear precipitation-vegetation feedback. A tight correspondence between a threshold level of Nile River runoff and the timing of occupation/abandonment of settlements suggests that along with climate changes in the eastern Sahara, the level of Nile River and intensity of summer floods were likely critical for the habitability of the Nile Valley (Egypt).