At a large scale, the human brain is organized into modules of interconnected regions, some of which play opposing roles in supporting cognition. In particular, the Default-Mode Network (DMN) has been linked to operations on internal representations, while task-positive networks are recruited during interactions with the external world. Here, we test the hypothesis that the generation of durable long-term memories depends on optimal recruitment of such antagonistic large-scale networks. As long-term memory consolidation is a process ongoing for days and weeks after an experience, we propose that individuals characterized by strong decoupling of the DMN and task-positive networks at rest operate in a mode beneficial for the long-term stabilization of episodic memories. To capture network connectivity unaffected by transient task demands and representative of brain behavior outside an experimental setting, 87 participants were scanned during rest before performing an associative encoding task. To link individual resting-state functional connectivity patterns to time-dependent memory consolidation processes, participants were given an unannounced memory test, either after a brief interval or after a retention period of ˜6 weeks. We found that participants with a resting state characterized by high synchronicity in a DMN-centered network system and low synchronicity between task-positive networks showed superior recollection weeks after encoding. These relationships were not observed for information probed only hours after encoding. Furthermore, the two network systems were found to be anticorrelated. Our results suggest that this memory-relevant antagonism between DMN and task-positive networks is maintained through complex regulatory interactions between the systems.