The objective of this study is to assess the occurrence, spatial, and temporal distribution of forty-eight multiclass pesticides in surface and groundwater samples of the Abou Ali River, located in the North of Lebanon. A 3-year monitoring program (six batches from August 2015 to March 2017) was implemented, and thirty sampling points were selected along the river for analysis. The analysis was executed using a previously developed and optimized solid-phase micro-extraction (SPME) gas-chromatography-mass spectrometry (GC-MS) method. Statistical analysis, using Kolmogorov-Smirnov, Kruskal-Wallis, and Dunnet T3 multiple comparison tests, was applied to compare mean concentrations of pesticides between the different sampling sites and the batches taken. The pesticides that had the highest frequency of detection in the surface and groundwater samples were alachlor, α-endosulfan, and methomyl. For surface water samples, high mean concentrations were perceived for two stations in the upper stream (S5 and S7), two stations (S11 and S14) in the middle stream, and one station (S16) in the lower stream of the river. The highest mean concentrations were observed in October 2015 and August 2016, the time of the year which correlates with the period of pesticide application. Considering groundwater samples, high mean concentrations of pesticides were detected in sites G4, G9, G10, and G12 and during October 2015 and March 2016, following the rainy season. Ecotoxicological risk assessment using the risk quotient (RQ) methodology revealed high risk for five pesticides under average conditions and fourteen under extreme conditions. This study presents, for the first time, a statistical analysis showing the quantification of pesticides in the water resources of the Abou Ali River. In conclusion, it reveals the need to apply a complete pesticide monitoring program, not only for the Abou Ali River but for all the water resources in Lebanon.