Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. SE sensitization contributes to T 2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.