Multicultural adolescents (MA) in Korea experience higher depression and lower life satisfaction compared to Korean native adolescents. To consider appropriate interventions, this study investigates the cross-lagged effect between life satisfaction and depression among these adolescents. Secondary data from the Multicultural Adolescents Panel Survey, which is a nationally representative sample, was analyzed. Data from the 3rd (T1, elementary school), 5th (T2, middle school), and 7th (T3, high school) waves (2013–2017) were used. Altogether, 1,239 MA were included in the sample for analysis; the mean age at T1 was 11.97 (± 0.36) years. The ten-item Depression Scale Questionnaire was used to measure depression, and the three-item Happiness Scale was used to measure life satisfaction. The random intercept cross-lagged panel model was conducted to estimate within-person autoregressive and cross-lagged effects. Life satisfaction and depression had a reciprocal relationship from T1 to T2, while only life satisfaction had a lagged effect from T2 to T3. Life satisfaction’s lagged effect dominated that of depression. The cross-lagged effect size of depression from T1 to T2 was larger than that from T2 to T3, and that of life satisfaction from T2 to T3 was larger than that from T1 to T2. Low life satisfaction in MA continues over time. Depression is not persistent, but if experienced in elementary school, it leads to low life satisfaction in middle school and depression in high school. The findings suggest that early intervention for depression in elementary school can reduce its negative effect MA’s life satisfaction.