Chromato–mass spectrometry has been applied to investigate technical lewisite containing α- and β-isomers, each containing the respective stereoisomers. The mass spectra of positive ions of the stereoisomers have been practically identical, whereas substantial differences have been observed in the negative ion mass spectra. Using quantum-chemical simulation at the B3LYP/6-311+G(d,p) level, the relative stability of the isomers, bonds dissociation energy, electron affinity, and ionization energy have been estimated. The formation of characteristic negative ions from the cis-isomer of α-lewisite and their absence for the trans-isomer is shown to be driven by the steric factors affecting the rearrangement processes.