The COVID-19 pandemic was stressful for many adolescents and their families, but effects proved far from uniform. Using a person-centered approach, this study aimed to identify types of perceived changes in family climate during the pandemic’s first lockdown, and test risk and resilience factors for differential changes in family climate. Further, risk and protective factors regarding longitudinal changes in adolescents’ well-being were tested depending on family climate. The longitudinal analyses included 822 adolescent participants (age 16–20; 42.7% male) from the German Family Panel pairfam, who were assessed in 2018/2019 and in early summer 2020. Latent Class Analysis revealed three classes of perceived changes in family climate (58% stable, 14% improvement, 28% deterioration). Adolescents’ older age, parental separation, and financial difficulties were connected to a deterioration in family climate. Findings revealed predominantly negative changes in adolescents’ well-being, i.e., increased loneliness and reduced activity, but also reduced stress. Adolescents with a perceived deterioration in family climate experienced a substantial decline in well-being compared to the other classes. Factors like female gender and isolation from peers emerged as risk factors for adolescent well-being. Additional analyses within classes revealed strongest or exclusive effects of risk and protective factors on adolescents’ loneliness in the deterioration class. Findings point towards the important role of family dynamics for adolescent well-being in the context of crises. Interventions targeting adolescents should consider the negative consequences of the pandemic for the whole family system but also acknowledge that the lockdown did not only have negative effects.