Comprehensive assessment of the aquatic fate and effects of organic micropollutants is greatly hindered by the need to develop compound-specific methodologies prior to sampling and analysis. A data-driven workflow, coupling high-resolution, accurate-mass (HRAM) mass spectrometry and highly sensitive online solid phase extraction (SPE) analysis, ensures complete characterization of organic pollutants in aquatic environments. In this work, water samples collected from a coastal golf course community were screened for the presence of trace organic contaminants by a non-targeted HPLC–HRAM mass spectrometry workflow. The occurrence of identified and confirmed contaminants was then quantitatively assessed by a high-throughput online SPE LC-MS/MS method.