Preterm birth predisposes children to internalizing and externalizing behaviors that may persist into adolescence resulting in adult mental health conditions. Social and caregiving contexts, particularly for vulnerable infants born preterm, influence long-term outcomes, but mechanisms are not clearly understood. Healthcare teams caring for those born preterm face difficulty predicting who will be most affected by risk, who will most benefit, and the optimal timing of intervention. Differential susceptibility theory offers an alternative to the traditional risk-only assessments and theories by positing that individuals may be more, or less, susceptible to environmental influences. A sample of preterm- and term-born infants were followed from birth to 23 years of age. Mixed model repeated measures analyses of internalizing and externalizing behaviors were utilized for the comparison groups (N = 214; observations = 1070). Environmental contexts were indexed as proximal protection (low, moderate, high) and medical risk (low, moderate, high). Personal characteristic covariates of sex, race, socioeconomic status, and cognition were modeled. Internalizing behavior trajectories varied significantly over time. Early proximal protective environments conferred a sustained positive influence on behaviors. There is partial support for differential susceptibility theory suggesting that prematurity, as a malleability characteristic enables absorption of both the positive and negative influences of the environment, with greater intensity that those without malleability. The current analyses suggest lasting effects of the preschool age proximal environment on internalizing and externalizing behaviors in young adulthood for those born preterm. Understanding these nuances may aid healthcare professionals in the promotion and timing of interventions to support the child and family. The current manuscript reflects ongoing analyses of longitudinal data. No patient or public contribution to the analyses were required for testing the differential susceptibility theory. The authors would solicit patient or public contribution when implementing practice or policy changes based on the results., (© 2022 Wiley Periodicals LLC.)