This study examined changes in adolescents’ perceived relationship quality with mothers and fathers from middle school to high school, gender differences, and associated mental health consequences using longitudinal data from the New England Study of Suburban Youth cohort (n = 262, 48% female) with annual assessments (Grades 6–12). For both parents, alienation increased, and trust and communication decreased from middle school to high school, with greater changes among girls. Overall, closeness to mothers was higher than with fathers. Girls, compared to boys, perceived more trust and communication and similar levels of alienation with mothers at Grade 6. Girls perceived stronger increases in alienation from both parents and stronger declines in trust with mothers during middle school. Increasing alienation from both parents and less trust with mothers at Grade 6 was associated with higher levels of anxiety at Grade 12. Less trust with both parents at Grade 6 and increasing alienation and decreasing trust with mothers in high school were associated with higher levels of depressive symptoms at Grade 12. Overall, girls reported having higher levels of anxiety at Grade 12 compared to boys. Findings on the course of the quality of parent–adolescent relationships over time are discussed in terms of implications for more targeted research and interventions.