The present study applies a multilevel approach to an examination of the effect of two randomized preventive interventions with mothers in neglectful families who are also contending with elevated levels of impoverishment and ecological risk. Specifically, we examined how participation in either child–parent psychotherapy (CPP) or psychoeducational parenting intervention (PPI) was associated with reductions in maternal psychological parenting stress and in turn physiological stress system functioning when compared to mothers involved in standard community services as well as a demographic comparison group of nonmaltreating mothers. The resulting group sizes in the current investigation were 44 for CPP, 34 for PPI, 27 for community services, and 52 for nonmaltreating mothers. Mothers and their 13-month-old infants were randomly assigned to intervention group at baseline. Mothers completed assessments on stress within the parenting role at baseline and postintervention. Basal cortisol was sampled at postintervention and 1-year follow-up. Latent difference score analyses examined change in these constructs over time. Results suggested that mothers within the CPP intervention experienced significant declines in child-related parenting stress, while mothers in the PPI intervention reported declines in parent-related parenting stress. In turn, significant decreases in stress within the CPP mothers were further associated with adaptive basal cortisol functioning at 1-year postintervention. The results highlight the value of delineating how participation in preventive interventions aimed at ameliorating child maltreatment in neglectful families within the context of poverty may operate through improvements in psychological and physiological stress functioning. Findings are discussed with respect to the importance of multilevel assessments of intervention process and outcome.