Mother–infant synchrony is one of the most important processes in the development of socio-affective competencies in children. While maternal abilities and psychopathology are related to maladaptive mother–infant synchrony, it is as yet unclear how maternal emotion regulation difficulties contribute to it. Based on a panel of behavioral indicators (i.e., gaze, vocal, and motor), the present study examined mother–infant synchrony at 6 months of age in a modified version of Ainsworth's Strange Situation (n = 72 dyads). Mother–infant interaction sequences were characterized by indicators of complexity (LZ complexity of joint behavioral sequences) and of synchronization quality (cross-recurrence plot quantification). Results showed that mothers’ touch was greater in the reunion condition than in the initial condition. Mothers’ motor behaviors were associated with the global levels of infants’ behavioral involvement in the reunion condition, unlike the symmetrical influence observed between mothers and infants in the initial condition. Results show that maternal anxiety mediates the relationships between mothers’ emotion regulation difficulties and gaze, vocal, and motor synchrony between mothers and infants in the initial and reunion conditions. This study emphasizes the central role of maternal emotion regulation difficulties in the establishment of maladaptive synchrony and in the adjustments of maternal physical contacts with infants.