Abstract We experience countless pieces of new information each day, but remembering them later depends on firmly instilling memory storage in the brain. Numerous studies have implicated non-rapid eye movement (NREM) sleep in consolidating memories via interactions between hippocampus and cortex. However, the temporal dynamics of this hippocampal-cortical communication and the concomitant neural oscillations during memory reactivations remains unclear. To address this issue, the present study used the procedure of targeted memory reactivation (TMR) following learning of object-location associations to selectively reactivate memories during human NREM sleep. Cortical pattern reactivation and hippocampal-cortical coupling were measured with intracranial EEG recordings in patients with epilepsy. We found that TMR produced variable amounts of memory enhancement across a set of object-location associations. Successful TMR increased hippocampal ripples and cortical spindles, apparent during two discrete sweeps of reactivation. The first reactivation sweep was accompanied by increased hippocampal-cortical communication and hippocampal ripple events coupled to local cortical activity (cortical ripples and high-frequency broadband activity). In contrast, hippocampal-cortical coupling decreased during the second sweep, while increased cortical spindle activity indicated continued cortical processing to achieve long-term storage. Taken together, our findings show how dynamic patterns of item-level reactivation and hippocampal-cortical communication support memory enhancement during NREM sleep.