The Damietta branch of the River Nile is the main source of drinking and irrigation water for the El-Qalubia, El Dakhlyia, and Damietta governorates. It receives various types of pollutants, such as industrial and agricultural waste, as well as sewage, which have negative effects on water quality and human health. This study was designed to investigate the potential variations in the quality of surface water in this branch of the Nile River. The study focused on five stations (El-Kanater El-Khayria, Benha, Zefta, Talkha, and El-Serw) and analyzed the physico-chemical characteristics, as well as some heavy metals (Fe, Mn, Zn, Cu, Ni, Co, Pb, Cd, and Cr). The findings of the current study indicated that the physico-chemical parameters and heavy metal concentrations in the water of the examined stations were within the acceptable limits. Notably, El-Serw station exhibited the highest levels of BOD, COD, Cl, SO₄, CO₃, and HCO₃. Additionally, El-Kanater El-Khayria station displayed the highest concentration of SiO₂. Furthermore, a strong positive correlation was observed among the majority of the parameters. The concentrations of the studied heavy metals in water were found to be below the permissible levels of the Egyptian standards. Among the heavy metals, the highest levels of Fe, Zn, Cu, Ni, Co, Pb, and Cd were observed at Talkha station, while the highest concentration of Cr was recorded at El-Serw station. It is worth noting that all the heavy metals studied showed a positive correlation with each other.