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Current theories suggest that memories for novel information and events, over time and with repeated retrieval, lose the association to their initial learning context. They are consolidated into a more stable form and transformed into semantic knowledge, that is, semanticized. Novel, related information can then be rapidly integrated into such knowledge, leading to superior memory. We tested these hypotheses in a longitudinal, 302-day, human functional magnetic resonance imaging study in which participants first overlearned and consolidated associative structures. This phase was associated with a shift from hippocampal- to ventrolateral prefrontal cortex (vlPFC)-mediated retrieval, consistent with semanticization. Next, participants encoded novel, related information whose encoding into the already acquired knowledge was orchestrated by the ventromedial prefrontal cortex. Novel related information exhibited reduced forgetting compared with novel control information, which corresponded to a faster shift from hippocampal- to vlPFC-mediated retrieval. In sum, the current results suggest that memory for novel information can be enhanced by anchoring it to prior knowledge via acceleration of the processes observed during semanticization.