The current study examined interactions among genetic influences and children’s early environments on their development of externalizing behaviors during the formative early childhood years. The sample included 361 families linked through adoption (birth parents and adoptive families). Data were collected when the children were ages 9, 18, and 27 months, and 4.5 and 6 years old. Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home (exposure to center-based Early Care and Education programs; ECE). Overreactive parenting predicted more externalizing behaviors as a time-varying predictor. Attending center-based ECE was associated with increasing externalizing behaviors only for children with a genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of over-reactive parenting on externalizing behavior than other children.