Acetyl-coenzyme A carboxylase (ACCase) has been identified as one of the most important targets of herbicide Aryloxyphenoxypropionates (APPs). ACCase shows different enantioselectivity toward APPs, and only (R)-enantiomers of APPs have the herbicidal activity. In order to deeply understand the enantioselective recognition mechanism of ACCase, (R)-haloxyfop, which is a typical commercial herbicide from APPs, is selected and the relative binding free energy between ACCase and (R)-haloxyfop is investigated and compared with that between ACCase and (S)-haloxyfop by homology modeling and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method. Further free energy analysis reveals that the preference of ACCase toward (R)-haloxyfop is mainly driven by Van der Waals interaction. The analysis of the interaction between the active site residues of ACCase CT domain and (R)-haloxyfop shows the van der Waals interactions have a close relationship with the addition effect of each residue. An understanding of the enantioselective recognition mechanism between ACCase and haloxyfop is desirable to discover novel chiral herbicides.