Caring for adolescents with congenital heart disease requires attention to physical health but also to psychosocial functioning. Identifying how such psychosocial variables influence one another over time is important for designing health care strategies. The present study examined how depressive symptoms, loneliness, paternal and maternal support, and quality of life predicted one another. A total of 429 mid- to late adolescents with congenital heart disease (53.4 % boys) participated in a three-wave longitudinal study. Cross-lagged analyses indicated that depressive symptoms and loneliness mutually reinforced one another over time and led to relative decreases in quality of life. Paternal- and not so much maternal-support predicted relative decreases in depressive symptoms and loneliness and relative increases in quality of life. Maternal and paternal support, in turn, were negatively predicted by previous levels of adolescent depressive symptoms. In sum, important temporal sequences were uncovered potentially providing information for prevention and intervention targeting psychosocial functioning in adolescents with congenital heart disease.