Water contamination by mutagenic microchemicals is a worldwide problem. To evaluate the overall water quality and identify the source(s) of pollutants (B, Fe, Cu, Mn, Ni, Pb, Cd, and Cr) in different watercourses in middle-upper Egypt, we analyzed 66 surface water samples collected from the significant waterways. In addition to trace pollutants, 15 physicochemical parameters (pH, Temperature, EC, alkalinity, DO, BOD, COD, Ca2+, Mg2+, Na+, K+, HCO3 -, SO4 2-, Cl-, and NO3 -) were measured. Multivariate statistical approaches such as exploratory principal component analysis, hierarchical cluster analysis, and correlation matrix analysis were applied to explore the sources of the contaminants. Data reveal that surface water quality in the investigated area is threatened by high concentrations of trace elements, which are higher than the permissible limits recommended by WHO guidelines and Egyptian standards for drinking water and irrigation purposes. Statistical analyses suggest that surface water contamination is the result of interference of natural (geogenic related to rock–water interaction) and human (interrelated to agrogenic and domestic sewage) inputs. The study will help decision-makers to take appropriate actions for freshwater sustainable management and protection. Moreover, surface water should be treated before use for drinking purposes.