Benzothiazoles, benzotriazoles and benzosulfonamides are high-production-volume chemicals found in various environmental aqueous samples that should be considered as emerging pollutants. This study examines the suitability of comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC x GC-TOF-MS) for the characterization of benzothiazoles, benzotriazoles and benzosulfonamides in aqueous matrices. Solid-phase extraction was optimized in order to ensure the proper preconcentration of these contaminants prior to their analysis. Column selection, in both the first and second dimensions, was optimized to ensure a good chromatographic separation of the target analytes and of the potential interfering compounds extracted from the matrix. Several column phases were tested. The combined power of two-dimensional separation was fully illustrated by identifying minor compounds and avoiding the overestimations usually made by one-dimensional systems. Finally, the suitability of GC x GC-TOF-MS to quantify the aforementioned emerging pollutants was proven by determining those pollutants in several real samples such as river water, effluent from a wastewater treatment plant, and raw sewage.