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Academic stress is rising among high school students, especially in light of the Covid-19 pandemic, such as social distancing, long-term online learning, and lack of social support. Many studies have also shown that students with high levels of academic stress have a higher risk of depression. However, very few researchers are interested in studying life satisfaction as a moderate factor for the indirect relationship between academic stress and depression. This study investigated whether life satisfaction factors moderate the indirect effect of academic stress on the depressive disorder in Vietnam adolescents. Participants include 1336 Vietnamese adolescents. Participants completed the Educational Stress Scale for Adolescents, Connor–Davidson Resilience Scale, Satisfaction with Life Scale, and Beck Depression Inventory-II. Moderated mediation analyses were conducted using the PROCESS macro to investigate the relationship among variables. In the relationship between academic stress and depressive disorder in Vietnamese adolescents, resilience is partly mediated; life satisfaction significantly moderated the indirect effect of academic stress on depressive disorder. This study suggests that depressive disorders prevention and intervention practices for adolescents need to consider enhancing resilience and life satisfaction.