The hydrophobically driven inclusion complexation of the Chemical Warfare Agent (CWA) pinacolyl methylphosphonofluoridate (soman, or GD) by β-cyclodextrin (β-CD) is studied both experimentally and computationally. Semiempirical modelling (PM6) adds further insight to the understanding of the CD–GD complex and the preferential binding of P(+) isomers over P(−). Comparison of the CD–GD complex to those formed by β-CD with commonly used trialkyl phosphate and dialkyl methylphosphonate simulants furnishes preliminary supramolecular agent–simulant correlation data. Such comparison studies will have utility in the design of new CWA-responsive materials.