A single multiresidue method was developed to determine 109 priority organic compounds included in the 76/464/EEC Council Directive on Pollution of the European Union. Such Directive includes 132 priority pollutants with a broad spectrum of polarities to be analyzed in drinking and surface waters, with the aim to protect water quality. From this list, the compounds analyzed included benzidines, chloroanilines, chloronitrobenzenes, chloronitrotoluenes, chlorophenols, chloronitrotoluidines, PAHs, PCBs, pesticides, phenylurea, and triazine herbicides. The method was developed in four steps. First, automated off-line solid-phase extraction using polymeric sorbent Oasis 60 mg cartridges was optimized to trap 109 compounds. Second, gas chromatography coupled to mass spectrometry with electron impact ionization (GC/EI/MS) was used in selected ion monitoring (SIM) mode for tentative identification of target analytes. Third, GC/EI/MS under full scan conditions was used for spectrum identification and analyte confirmation. Last, quantification was performed from SIM chromatogram using surrogates and internal standard. This method offered excellent sensitivity and selectivity, and the preconcentration of 200 mL permitted the achievement of limits of detection at the low nanogram/liter level and recoveries between 70 and 120%. Such methodology was applied to determine 109 organic compounds in French surface waters, and several pollutants were detected at levels from ppt to ppb. This multiresidue method developed was highly reproducible and robust and permitted a high sample throughput.