The fundamental interactions of a series of chemical warfare agent (CWA) simulants on amorphous silica particulates have been investigated with transmission infrared spectroscopy and temperature-programmed desorption (TPD). The simulants methyl dichlorophosphate (MDCP), dimethyl cholorophosphate (DMCP), trimethyl phosphate (TMP), dimethyl methylphosphonate (DMMP), and diisopropyl methylphosphonate (DIMP) were chosen to help develop a comprehensive understanding for how the structure and functionality of CWA surrogate compounds affect uptake and hydrogen-bond strengths at the gas–surface interface. Each simulant was found to adsorb molecularly to silica through the formation of strong hydrogen bonds primarily between isolated surface silanol groups and the oxygen atom of the P═O moiety in the adsorbate. The TPD data revealed that the activation energy for desorption of a single simulant molecule from amorphous silica varied slightly with coverage. In the limit of zero coverage and the absence of significant surface defects, the activation energies for desorption were found to follow the trend MDCP < DMCP < TMP < DMMP < DIMP. This trend demonstrates the critical role of electron-withdrawing substituents in determining the adsorption energies through hydrogen-bonding interactions. The infrared spectra for each adsorbed species, recorded during uptake, showed a significant shift in the frequency of the ν(SiO–H) mode as the hydrogen bonds formed. A clear linear relationship between the desorption energy and the shift of the surface ν(SiO–H) mode across this series of adsorbates demonstrates that the Badger–Bauer relationship, established origninally for solute–solvent interactions, effectively extends to gas–surface interactions. High-level electronic structure calculations, including extrapolation to the complete basis set limit, reproduce the experimental energies of all simulants with high levels of accuracy and have been employed to provide insight into the molecular-level details of adsorption geometries for the simulants and to predict the interaction energies for the CWA isopropyl methylphosphonofluoridate (sarin).