Interacting with others by interpreting and responding to their facial expressions is an essential and early developing social skill in humans. We examined whether and how variation in catechol-O-methyltransferase (COMT) and serotonin transporter (5-HTTLPR) genes is associated with 7-month-old infants’ electrocortical responses to facial expressions. The results revealed that COMT variants are associated with differences in infants’ brain responses to fearful faces over centro-parietal regions, whereas 5-HTTLPR variants are associated with differences in infants’ brain responses to happy faces over fronto-temporal regions. Further support for differential associations of these gene variants with emotional processing came from our analysis of infant behavioral temperament: variation in COMT was associated with differences in infants’ recovery from distress, whereas variation in 5-HTTLPR was associated with infants’ smiling and laughter. This pattern of findings indicates that, in infancy, these genetic variants influence distinct brain systems involved in the processing of either positive or negative emotions. This has wide reaching implications for our understanding of how genetic variation biases specific brain mechanisms, giving rise to individual differences in emotional sensitivity and temperament.