Although stress strongly predicts life satisfaction, the psychosocial mechanisms underlying this association remain unclear. To investigate the possible mediating role of coping, we conducted a cross-sectional study that assessed youths' life stress levels, propensity to engage in three different coping styles (i.e., active coping, internal coping, & withdrawal), ​and life satisfaction in a probabilistic, two-stage stratified cluster sample of 1830 high school seniors (986 females; age range: 17–22 years old) from 26 schools in or around the four largest cities in Croatia. We used correlational analyses and structural equation modelling to test the hypothesis that coping mediates the relation between stress and life satisfaction. The tested model was marginally acceptable: χ2 = 1613.85, df = 177, p < 0.001, goodness-of-fit-index = 0.92, Comparative Fit Index = 0.91, Tucker-Lewis Index = 0.89, root mean square error of approximation = 0.067 (90% CI = 0.064 to 0.070), standardized root mean squared residual = 0.056. As hypothesized, stress was related to life satisfaction directly (βc’ = −0.22, p < 0.01) but also indirectly (βab = −0.05, p < 0.01) by affecting youths' likelihood of engaging in withdrawal behaviours, such as avoiding problems, distracting, or using anger, alcohol, or drugs. The proportion of the total effect mediated by withdrawal was 19.4%. In contrast, neither active nor internal coping were significant mediators. Based on these results, we conclude that preventive and educational programs for enhancing youth mental health may benefit from reducing adolescents' stress levels and stress-related withdrawal behaviour, and by encouraging youth to use active coping strategies instead.