This study investigated the longitudinal associations among prenatal substance use, socioeconomic adversity, parenting (maternal warmth, sensitivity, and harshness), children's self-regulation (internalization of rules and conscience), and conduct problems from infancy to middle childhood (Grade 2). Three competing conceptual models including cascade (indirect or mediated), additive (cumulative), and transactional (bidirectional) effects were tested and compared. The sample consisted of 216 low-income families (primary caretaker and children; 51% girls; 74% African American). Using a repeated-measures, multimethod, multi-informant design, a series of full panel models were specified. Findings primarily supported a developmental cascade model, and there was some support for additive effects. More specifically, maternal prenatal substance use and socioeconomic adversity in infancy were prospectively associated with lower levels of maternal sensitivity. Subsequently, lower maternal sensitivity was associated with decreases in children's conscience in early childhood, and in turn, lower conscience predicted increases in teacher-reported conduct problems in middle childhood. There was also a second pathway from sustained maternal depression (in infancy and toddlerhood) to early childhood conduct problems. These findings demonstrated how processes of risk and resilience collectively contributed to children's early onset conduct problems.