The amygdala is critically involved in emotional processing, including fear responses, and shows hyperactivity in anxiety disorders. Previous research in healthy participants has indicated that amygdala activity is down-regulated by cognitively demanding tasks that engage the PFC. It is unknown, however, if such an acute down-regulation of amygdala activity might correlate with reduced fear in anxious participants. In an fMRI study of 43 participants (11 men) with fear of snakes, we found reduced amygdala activity when visual stimuli were processed under high cognitive load, irrespective of whether the stimuli were of neutral or phobic content. Furthermore, dynamic causal modeling revealed that this general reduction in amygdala activity was partially mediated by a load-dependent increase in dorsolateral PFC activity. Importantly, high cognitive load also resulted in an acute decrease in perceived phobic fear while viewing the fearful stimuli. In conclusion, our data indicate that a cognitively demanding task results in a top–down regulation of amygdala activity and an acute reduction of fear in phobic participants. These findings may inspire the development of novel psychological intervention approaches aimed at reducing fear in anxiety disorders.