A method using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography/mass spectrometry (GC/MS) analysis has been developed to gain insight into the degradation of the chemical warfare agent sulfur mustard in solution. Specifically, the described approach simplifies the sample preparation for GC/MS analysis to provide a rapid determination of changes in sulfur mustard abundance. These results were found to be consistent with those obtained using liquid-liquid extraction (LLE) GC/MS. The utility of the described approach was further demonstrated by the investigation of the degradation process in a complex matrix with surfactant added to assist solvation of sulfur mustard. A more rapid reduction in sulfur mustard abundance was observed using the HS-SPME approach with surfactant present and was similar to results from LLE experiments. Significantly, this study demonstrates that HS-SPME can simplify the sample preparation for GC/MS analysis to monitor changes in sulfur mustard abundance in solution more rapidly, and with less solvent and reagent usage than LLE.