Increased acts of international terrorism called for the development of rapid and reliable chemical agent decontamination reactions to minimize human exposure and material loss. Even though many chemical reaction processes have been reported, most remain unattractive for various reasons. In order to eliminate many of the adversities, these processes were studied in an ionic liquid solvent. In this report, we describe the reaction between chemical warfare simulants with alcohols in the ionic liquid 1,2-dimethyl-3-propylimmidazolium bis(trifluoromethylsulfonyl)amide made basic with tetramethylammonium hydroxide pentahydrate. The chemical agent simulants used in this study were diisopropylfluorophosphate, bis(2-ethylhexyl) phosphite, and chloroethylphenyl sulfide, which simulate agents GD, VX, and HD, respectively. The reactions were rapid, and products were identified by LC/MS-TOF and GUMS. All of the reaction products of the VX and HD simulants remained in the ionic liquid, whereas the products from GD simulant partitioned between the ionic liquid and water extract.