Down-regulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive Transcranial Magnetic Stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. In this study, we aimed to test an rTMS procedure over the aPFC to long-term down-regulate the defensive responses toward threat-predictive stimuli in humans. Participants underwent a threat learning procedure. A week later, one group was stimulated over the aPFC, while the other conditions were stimulated over the occipital cortex (OC), the dorsolateral PFC (dlPFC), or sham-stimulated. Immediately afterward, participants underwent implicit or explicit recognition tests. A further week later, participants were re-tested in a follow-up session for the potential endurance of rTMS effects over time. We found that rTMS over the aPFC immediately decreased implicit reactions to learned and new stimuli. These effects enduringly persisted one week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dlPFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement towards the long-term deactivation of exaggerated responses to threats.