Neural synchronization between distant cell assemblies is crucial for the formation of new memories. To date, however, it remains unclear whether higher-order brain regions can adaptively regulate neural synchrony to control memory processing in humans. We explored this question in two experiments using a voluntary forgetting task. In the first experiment, we simultaneously recorded electroencephalography along with fMRI. The results show that a reduction in neural synchrony goes hand-in-hand with a BOLD signal increase in the left dorsolateral prefrontal cortex (dlPFC) when participants are cued to forget previously studied information. In the second experiment, we directly stimulated the left dlPFC with repetitive transcranial magnetic stimulation during the same task, and show that such stimulation specifically boosts the behavioral forgetting effect and induces a reduction in neural synchrony. These results suggest that prefrontally driven downregulation of long-range neural synchronization mediates goal-directed forgetting of long-term memories.