Sulfur mustard (SM) is recognized as one of the most lethal warfare agents. It has the potential to seriously affect public health and safety. To employ appropriate medical countermeasures and treat victims as quickly as possible, the development of a rapid and simple SM detection technique is crucial. The aim of the present study was to explore novel detection systems exhibiting excellent selectivity and high sensitivity. An SM probe, namely N-(rhodamine-B)-thiolactam-2-n-butane (SRB-NB), which was based on a thiolactam structure, was effectively designed and synthesized. The rhodamine and thiourea moieties played the roles of the chromogenic and reacting groups, respectively. Subsequently, using ionic liquids (ILs) as the solvents, a turn-on fluorescence detection system was constructed. Notably, it was found that imidazole-based ILs displayed good solubility for an SM simulant, specifically 2-chloroethyl ethyl sulfide (2-CEES). Moreover, 1-butyl-3-methylimidazolium dicyandiamide ([BMIm]DCA) IL held the maximum amount of 2-CEES (132.5 g/100 g). The SRB-NB probe exhibited better ultraviolet (UV) absorption and fluorescence properties in ILs than in other organic solvents. SRB-NB/IL was able to detect 2-CEES in liquid form with remarkable selectivity and sensitivity. The limit of detection (LOD) was established at 3.0 × 10-6 M. Importantly, SRB-NB/ILs also showed good optical response to gaseous 2-CEES and SM.