In Egypt, the shortage of freshwater resources and their pollution constitutes a growing concern. Therefore, the objectives of this study were to (i) monitor the occurrence and spatiotemporal variations of 100 pesticides in surface water samples collected monthly (from July 2018 to June 2019) from El-Rahawy, Sabal, and Tala sampling sites along the Rosetta branch of the River Nile in Egypt, (ii) identify potential noncarcinogenic health risks for the local people through the lifetime consumption of contaminated drinking water, and (iii) perform an ecological risk assessment of aquatic organisms upon exposure to pesticides detected in surface waters based on the risk quotients (RQs) method. Of the 100 pesticides analyzed, 22 belonging to 11 chemical families were detected, and 75.5% of surface water samples were contaminated with one or more pesticide residues. The most frequently detected pesticide was malathion (57%), followed by chlorpyrifos (54%), atrazine (23%), and carbendazim (20%). Spatial distribution showed that the El-Rahawy site had the highest pesticide load (38.47 µg/L), and Sabal had the lowest (16.29 µg/L). Temporal variations revealed that the highest total pesticide concentrations were detected in summer (27.98 µg/L) compared to spring (23.16 µg/L), winter (19.18 µg/L), and autumn (11.85 µg/L). For non-carcinogenic risks of pesticides detected in surface water, the target hazard quotient (THQ) values were less than one. This implies that there is no potential human risk from exposure to drinking water at the sites under study. However, 13 pesticides presented high-risk quotients (RQ > 1), posing potential ecological risks to aquatic organisms.