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Mother-infant interactions, including culturally specific features, have been found to predict child socio-emotional development (e.g., social communication and emotion regulation (ER)). However, research is lacking on the specific processes involved. We used a cross-cultural, longitudinal design, and a microanalytic coding approach to address this issue. Fifty-two mother-infant dyads were recruited from the UK ( N = 21) and Italy ( N = 31), representing Northern European and Mediterranean cultures, respectively. While these cultures share core features of parent-child relationships, their values about emotional expressiveness differ. We observed face-to-face mother-infant interactions at 2 months (T1), and coded infant socio-emotional behavior and maternal responses. Children were seen again at 2 years (T2), when their ER in the face of frustration, using the Barrier Task, was assessed, and the occurrence of different “mature” strategies (communicative and autonomous) coded. Results revealed common features of interactions at T1 (infant socio-emotional expressions, and maternal positive responses), but also cultural variation in the frequency of different infant cues (more pre-speech in UK infants, more smiles in Italians), and of maternal responses to them. While greater overall maternal responsiveness at T1 predicted more mature ER in general at T2, cultural differences in early responsiveness to specific infant behaviors predicted later group differences in children’s use of particular ER strategies, with UK children using more communicative strategies, and Italians more autonomous. Findings indicate that positive maternal behaviors that are common across cultures (e.g., responsiveness) promote overall successful child emotion regulation, while culturally specific features of interactions are associated with how child socio-emotional outcomes are expressed.