Focusing on the period of 54-months (i.e., 4.5 years) through age 15, the current study explored the longitudinal influence of early childhood relational adversity (i.e., low-quality mother-child relationship) on adolescents’ academic achievement and the moderating role of high-quality teacher-child interactions. Participants included 1077 children from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Academic success outcomes were obtained from official high school transcripts (i.e., grade point average at ninth grade) and direct assessments of adolescents’ cognitive abilities at age 15 (i.e., language, literacy, and mathematics). High-quality teacher-child interactions throughout elementary school (i.e., first grade, third grade, and fifth grade) were measured at the classroom level and assessed using an observational tool of emotional climate and classroom management. Analyses of data revealed a significant three-way interaction. High-quality teacher-child interactions throughout elementary school moderated the relation between early childhood relational adversity and adolescent math development for children from middle and upper-class families, but not for children from lower-class families. Furthermore, child gender was found to moderate the relation between high-quality teacher-child interactions and adolescent language development. Specifically, high-quality teacher-child interactions were positively associated with adolescent female language development but negatively associated with male language development. Implications for the findings, future research, academic programs, and interventions are discussed.