Exposure to mustard gas can cause damage or death to human beings, depending on the concentration and duration. Thus, developing high-performance mustard-gas sensors is highly needed for early warning. Herein, ultrathin WO 3 nanosheetsupported Pd nanoparticles hybrids (WO 3 NSs/Pd) are prepared as chemiresistive sulfur mustard simulant (e.g., 2-chloroethyl ethyl sulfide, 2-CEES) gas sensors. As a result, the optimal WO 3 NSs/Pd-2 (2 wt % of Pd)-based sensor exhibits a high response of 8.5 and a rapid response/recovery time of 9/92 s toward 700 ppb 2-CEES at 260 °C. The detection limit could be as low as 15 ppb with a response of 1.4. Moreover, WO 3 NSs/Pd-2 shows good repeatability, 30-day operating stability, and good selectivity. In WO 3 NSs/ Pd-2, ultrathin WO 3 NSs are rich in oxygen vacancies, offer more sites to adsorb oxygen species, and make their size close to or even within the thickness of the so-called electron depletion layer, thus inducing a large resistance change (response). Moreover, strong metal−support interactions (SMSIs) between WO 3 NSs and Pd nanoparticles enhance the catalytic redox reaction performance, thereby achieving a superior sensing performance toward 2-CEES. These findings in this work provide a new approach to optimize the sensing performance of a chemiresistive sensor by constructing SMSIs in ultrathin metal oxides.