Updating established memories in light of new information is fundamental for memory to guide future behavior. However, little is known about the brain mechanisms by which existing memories can be updated. Here, we combined functional magnetic resonance imaging and multivariate representational similarity analysis to elucidate the neural mechanisms underlying the updating of consolidated memories. To this end, participants first learned face–city name pairs. Twenty-four hours later, while lying in the MRI scanner, participants were required to update some of these associations, but not others, and to encode entirely new pairs. Updating success was tested again 24 h later. Our results showed increased activity of the dorsolateral prefrontal cortex (dlPFC) specifically during the updating of existing associations that was significantly stronger than when simple retrieval or new encoding was required. The updating-related activity of the dlPFC and its functional connectivity with the hippocampus were directly linked to updating success. Furthermore, neural similarity for updated items was markedly higher in the dlPFC and this increase in dlPFC neural similarity distinguished individuals with high updating performance from those with low updating performance. Together, these findings suggest a key role of the dlPFC, presumably in interaction with the hippocampus, in the updating of established memories.