Early life stress is associated with a host of social, emotional, cognitive, and behavioral difficulties for children later in life. These negative effects of early life stress are thought to be in part a consequence of chronic and/or extreme perceptions of stress leading to extended activation of physiological, psychological, and behavioral stress response systems, ultimately resulting in dysregulation in these systems. However, not all children who experience early life stress, even the same type of stressor, demonstrate later negative outcomes. It is important to understand the mechanisms that support individual differences in the outcomes of children exposed to early life stress in order to develop more effective targeted interventions for at-risk children and their families. The current work takes an integrative approach to addressing what factors underlie individual differences in children’s responses to early life stress, examining interactions among psychophysiological functioning, environmental factors, and children’s self-regulatory behaviors in the context of a preschool program targeting children exposed to early life stress. In Study 1, I demonstrate that children exhibit positive change in self-regulatory behaviors during the preschool program. Additionally, children’s patterns of behavior change are influenced by whether the child is living with their biological parents and whether they complete the program. In Study 2, I find that children’s parasympathetic cardiac regulation is related to their patterns of behavior change. Children with lower parasympathetic cardiac control at the start of the program initially demonstrate poorer self-regulatory behaviors but also have more pronounced positive change in these behaviors during the program. In addition, children’s parasympathetic cardiac regulation increases during the program, and these increases are associated with improvements in self-regulatory behaviors. Lastly, in Study 3, I examine changes in children’s behavior in response to the occurrence of a stressor (abuse, moving care, and parent arrest). I find, somewhat surprisingly, that children’s behavior improves after a parent arrest. After an occurrence of abuse, there are no immediate changes in children’s behavior, but children’s overall pattern of positive change in self-regulatory behaviors slows. Together this work illustrates the complex nature of interactions among children’s early environment, psychophysiological functioning, and their responses to early life stress. I discuss the implications of this work for understanding children’s immediate responses to stress, the influence of developmental patterns of psychophysiological change on these responses, and the role of individual differences in perceptions of environmental demands in children’s responses to stress.