To develop an easy and reliable method for detecting pesticides and their residues in the Mekong Delta, a GC-MS analytical method was developed and validated according to European guidelines (SANTE/11945/2015) for the determination of residues of three pesticides (quinalphos, trifluralin and dichlorvos) in water. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.002 and 0.007 μg/L, respectively, for quinalphos and trifluralin, and 0.016 and 0.053 μg/L, respectively, for dichlorvos and quinalphos. The repeatability, the within-laboratory reproducibility as well as the trueness met the European criteria. The recovery rate ranged between 72% (for dichlorvos and quinalphos) and 82% (for trifluralin). The developed method was then applied for the analysis of 33 water samples, collected in April 2013, at the beginning of the rainy season in the Mekong Delta in Vietnam. Thirteen samples were from rice field, 10 were collected from cat fish ponds and from red tilapia cages. Results showed that only 9% of total water samples analysed contained residues of pesticides, but only in water from rice fish systems. From the 13 samples taken in these systems, quinalphos was detected in three samples. The other two pesticides were not detected. A comparison between analytical results obtained from GC-MS and an alternative method, that is GC-ECD indicated that GC-ECD is less sensitive than GC-MS, with LOQ ranging from 0.37 to 1.18 (depending on the pesticide). However, for samples with concentrations above these LOQ, no significant difference was observed between the results obtained from the two analytical methodologies.