Abstract The functional interaction between hippocampo- and striato-cortical regions during motor sequence learning is essential to trigger optimal memory consolidation. Based on previous evidence from other memory domains that stress alters the balance between these systems, we investigated whether exposure to stress prior to motor learning modulates motor memory processes. Seventy-two healthy young individuals were exposed to a stressful or nonstressful control intervention prior to training on a motor sequence learning task in a magnetic resonance imaging (MRI) scanner. Consolidation was assessed with an MRI retest after a sleep episode. Behavioral results indicate that stress prior to learning did not influence motor performance. At the neural level, stress induced both a larger recruitment of sensorimotor regions and a greater disengagement of hippocampo-cortical networks during training. Brain-behavior regression analyses showed that while this stress-induced shift from (hippocampo-)fronto-parietal to motor networks was beneficial for initial performance, it was detrimental for consolidation. Our results provide the first experimental evidence that stress modulates the neural networks recruited during motor memory processing and therefore effectively unify concepts and mechanisms from diverse memory fields. Critically, our findings suggest that intersubject variability in brain responses to stress determines the impact of stress on motor learning and subsequent consolidation.