Newly acquired declarative memory traces are believed to be reactivated during NonREM sleep to promote their hippocampo-neocortical transfer for long-term storage. Yet it remains a major challenge to unravel the underlying neuronal mechanisms. Using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings in humans, we show that sleep spindles play a key role in the reactivation of memory-related neocortical representations. On separate days, participants either learned face-scene associations or performed a visuomotor control task. Spindle-coupled reactivation of brain regions representing the specific task stimuli was traced during subsequent NonREM sleep with EEG-informed fMRI. Relative to the control task, learning face-scene associations triggered a stronger combined activation of neocortical and hippocampal regions during subsequent sleep. Notably, reactivation did not only occur in temporal synchrony with spindle events but was tuned by ongoing variations in spindle amplitude. These learning-related increases in spindle-coupled neocortical activity were topographically specific because reactivation was restricted to the face- and scene-selective visual cortical areas previously activated during pre-sleep learning. Spindle-coupled hippocampal activation was stronger the better the participant had performed at prior learning. These results are in agreement with the notion that sleep spindles orchestrate the reactivation of new hippocampal-neocortical memories during sleep.