Ion mobility spectrometry with a corona discharge ionization source was employed to investigate the ionization mechanisms and quantitative determination of five sulfur-containing compounds with different structural and energetic properties, including methyl mercaptan, ethyl mercaptan, H₂S, CS₂, and COS. In addition, quantum chemical calculations using the G4MP2 method were performed to study the ionization reaction mechanisms. No signal was observed for H₂S, CS₂, and COS in positive polarity, whereas mercaptans were readily ionized in positive mode. Computational results showed that NO⁺ ions ionize mercaptans through charge transfer and hydride abstraction mechanisms. Therefore, oxygen was used as the drift gas to eliminate NO⁺ reactant ions, allowing ionization to proceed exclusively through proton transfer, which enhanced the main peak intensity while removing additional peaks. In negative polarity, only one common peak was observed for H₂S, CS₂, and COS, corresponding to the formation of the SO₂⁻ anion. Ion mobility spectrometry was also applied for the quantitative analysis of these compounds, and limits of detection (LOD) below 1 ppm were achieved. The detection limits ranged from 0.7 ppm for methyl mercaptan to 0.03 ppm for hydrogen sulfide. It was further demonstrated that natural gas alkanes, such as methane, are not ionized in the corona discharge ionization source and therefore do not interfere with the determination of sulfur-containing compounds.