A novel protocol for hydrolyzing phosphonothioate neurotoxins has been developed that uses a readily available, inexpensive and non-toxic molybdate (MoO42−). The target organophosphate is O,S-diethylphenyl phosphonothioate (1), a model compound that has served as an analog of the chemical warfare agent VX. Molybdate-mediated hydrolysis of 1 proceeds at room temperature (pH ∼ 7.5) and yields a relatively safe phosphonate product through P-S specific scission. This is the first report of utilizing the molybdate, MoO42−, to degrade an organophosphate neurotoxin with turnover. A ΔS‡ of −81.5 J/mol·K (−19.5 cal/mol·K) indicates a bimolecular process, and 18O-labeling studies show no oxygen exchange of 1 throughout the hydrolysis by MoO42−(aq). We hypothesize primarily the monomeric molybdate is the active species at pH 7.5 where a SN2(P) mechanism takes place. Density functional theory methods suggest the molybdate oxoanion serves as the nucleophile to attack phosphonothioate 1 to form a molybdate-phosphonate anhydride that subsequently hydrolyzes to the starting molybdate and phenylethyl phosphonate.