Itch is described as an unpleasant sensation, and chronic itch, such as that in atopic dermatitis (AD), often decreases a patient's QOL. There are few effective treatments for various chronic pruritic disorders that are not limited to inflammation. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used to treat some chronic pruritus disorders. However, there is little evidence from clinical and basic studies using animal models. In this study, we found that paroxetine suppressed acute and chronic itch in mouse models. Single administration of paroxetine (10 mg/kg) inhibited scratching behavior caused by histamine-dependent or histamine-independent itch. Moreover, paroxetine (10 mg/kg) inhibited spontaneous scratching behavior in AD model using NC/Nga mice without affecting locomotor function. These results suggest that paroxetine suppresses chronic itch caused by AD via histamine-dependent and -independent pathways. This study provides one of the few pieces of evidence that SSRIs suppress itch.