A rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method was developed for analysis of chemical transformation of 20(S)-protopanaxatriol (PPT)-type ginsenosides Re, Rg2, and Rf in acidic conditions. The transformation products were identified by comparing the retention time of the standard compounds, the accurate mass measurement, and the fragment ions obtained from RRLC-Q-TOF-tandem mass spectrometry (MS/MS) analyses. The specific product ions of aglycone PPT (m/z 475), C-24- and C-25-hydrated PPT (m/z 493), and Δ20(21) or Δ20(22) dehydration PPT (m/z 457) by MS/MS were discussed for structural characterization. Experiments demonstrated that chemical transformation mechanisms of 20(S)-PPT-type ginsenosides in acidic conditions include hydrolysis of saccharide substitution, Δ20(21) or Δ20(22) dehydration, and hydration addition reactions at C-24 and C-25. The chemical transformation pathway for 20(S)-PPT-type ginsenosides was summarized. The developed RRLC-Q-TOF-MS method was also applied for comparative analysis of 20(S)-PPT ginsenoside and related chemical transformation products in ginseng products.