The circadian rhythm, regulated by clock genes, plays a pivotal role in regulating physiological and behavioral processes, including mood regulation and alcohol consumption. Despite significant advancements in understanding the interplay between circadian dysregulation and affective disorders, the specific role of Bmal1 within the prefrontal cortex on modulating mood-like behaviors and alcohol binge drinking is not fully understood. This research aims to address this gap by investigating the effects of selectively deleting Bmal1 in the prefrontal cortex on these behavioral outcomes in male and female mice. Female Bmal1 knockout mice exhibited reduced depressive-like behaviors and heightened anxiety-like behaviors. This contrasted with male counterparts where no significant alterations in mood-related behaviors were observed. This study provides new perspectives into the role of Bmal1 in the prefrontal cortex in affective behavior and alcohol binge drinking male and female mice, emphasizes the importance of considering sex-specific responses.