Memory consolidation can be enhanced during sleep using targeted memory reactivation (TMR) and closed-loop (CL) acoustic stimulation on the up-phase of slow oscillations (SOs). Here, we test whether applying TMR at specific phases of the SOs (up vs. down vs. no reactivation) can influence the behavioral and neural correlates of motor memory consolidation in healthy young adults. Results show that up- (as compared to down-) state cueing results in greater performance improvement. Sleep electrophysiological data indicate that up- (as compared to down-) stimulated SOs exhibits higher amplitude and greater peak-nested sigma power. Task-related functional magnetic resonance images reveal that up-state cueing strengthens activity in - and segregation of - striato-motor and hippocampal networks; and that these modulations are related to the beneficial effect of TMR on sleep features and performance. Overall, these findings highlight the potential of CL-TMR to induce phase-specific modulations of motor performance, sleep oscillations and brain responses during motor memory consolidation.