Metal organic frameworks (MOFs) have been suggested as promising materials for application in the degradation of chemical warfare agents, with the majority of studies to date focusing on nerve agents. One of the most prominent MOFs used in the detoxification of nerve agents is UiO-66, which is of interest as a future nerve agent decontaminant. However, blister agents, which constitute one of the most toxic and highly reactive categories of chemical agents, are yet to be examined as gas-phase decontamination targets using MOF structures. In this study, a novel type of UiO-66 with a smaller particle size, namely, UiO-66S, was used as a decontaminant for the blister agent simulant, 2-chloroethyl ethyl sulfide (2-CEES). The gas-phase chemical adsorption and decomposition of 2-CEES were demonstrated for the first time, with an estimated t1/2 of 1.34 h. This value is the highest reported value for an MOF in gas-phase reaction conditions. The obtained nontoxic degradation products were identified, and the reaction mechanism was studied using density functional theory calculations. Furthermore, the synthesized UiO-66S catalyst also exhibits superior catalytic ability toward nerve agent simulants (diisopropyl fluorophosphate).The results of the study provide a firm basis for the use of UiO-66S as a future decontaminant for both nerve and blister agents.