A multi-determination method has been developed for the determination and confirmation of 68 organic pollutants in water samples by gas chromatography coupled to triple quadrupole mass spectrometry (GC-MS/MS). The following chemical families were determined in a chromatographic run of less than 26 min: polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenylethers (PBDEs), and pesticides (organochlorine, organophosphorus, triazine and others). The sample preparation involved a liquid-liquid extraction (LLE) procedure, obtaining recoveries ranging from 70 to 130% when dichloromethane was used as the extracting solvent. The detection limits of the proposed method were between 0.75 and 19.8 ng L−1. Samples from the Maipo River in central Chile were taken from 29 different points. Seven pesticides and two PAHs were detected in field collected samples with concentrations ranging from 10 to 95 ngL−1. Concentrations of benzo[a]pyrene in environmental samples ranged from 25 to 33 ngL−1 and were near the maximum levels established by the European Union Directives (50 ng L−1).