Small changes to the molecular structure of lubricant additives affect their adsorption and dissociation behaviour at the nanoscale, as well as their friction and wear performance at the macroscale. Here, we show using nonequilibrium molecular dynamics simulations with a reactive force field that secondary trialkylphosphates dissociate much faster than primary trialkylphosphates between sliding iron surfaces. For both molecules, dissociative chemisorption proceeds through cleavage of the carbon − oxygen bond. The rate increases exponentially with temperature and stress, which is indicative of a stress-augmented thermally activated process. Both molecules show similar activation energy and activation volume. The much higher reactivity of secondary trialkylphosphates is driven mostly by the pre-exponential factor, which is almost an order of magnitude larger than for primary trialkylphosphates. These observations and the associated kinetic parameters are consistent with recent macroscale tribometer experiments of the antiwear additive zinc dialkyldithiophosphate. This study represents a crucial step towards the virtual screening of lubricant additives with different substituents for optimal tribological performance.