River sediments are basic components of our environment, providing nutrients for living organisms and serving as sinks for deleterious chemical species. The metal contents may be remobilized and released back into waters with changes in environmental conditions, thus affecting living organisms and human activities. This paper aims to determine the effect of a synthetic anthropogenic chelating agent (EDTA) as industrial discharges on the remobilization of several metals (Cu, Zn, Cd, and Pb) in River Nile sediments (at Aswan and Mansoura cities) under different concentrations and pH values, and to investigate the influence of metal–EDTA complexes on this remobilization. For these purposes, sequential extraction and experiments on the effect of pH and metal EDTA complex were carried out on the two representative sediment samples south and north of the River Nile in Egypt. The results of sequential extraction show that most of metal contents present in the residual form (Cu, 11.36–72.34%; Pb, 29.64–66.67%; and Zn, 43.76–50.09% at Aswan and Mansoura, respectively). Non-residual fractions which may be available for the remobilization by EDTA represented anthropogenic (industrial, agriculture, and domestic discharges) and lithiopogenic (metals bound to Fe and Mn oxides) sources. A clear increase was detected for Cu and Zn remobilization from the increase in EDTA concentrations, in contrast, Cd independent of the EDTA concentration and slight influence on Pb content. The remobilization of metals as a function of pH exhibited. The metals were greatly remobilized under the complexing action of EDTA, showing that some of these elements were adsorbed on the sediments. The remobilization rate of metals was dependent upon the added metal–EDTA complex (with the exchange rate being in the order Ca–EDTA>Zn–EDTA>Cd–EDTA>Cu–EDTA>Pb–EDTA), due to the stability constant of the metal–EDTA complex. The results of these experiments showed that heavy metals are greatly remobilized under the complexing action of EDTA when it is present in excess, so all precautions should be taken to prevent any wastewater containing EDTA or any chelating agents discharging directly or indirectly via the River Nile stream because most EDTA remains in the aquatic phase. The ability of this portion to remobilize metals from sediments should be taken into account.