The aim of the present longitudinal study was to identify malleable factors during the last year of high school that predicted post-school outcomes in autistic youth one year after high school graduation. We then explored whether depressive symptoms in high school mediated the associations between other malleable factors and post-school outcomes. Thirty-two autistic youth and a parent completed surveys during the youth’s final year of high school (T1) and one-year post-high school graduation (T2). Malleable factors measured at T1 included social communication skills, executive functions, responsibility for daily tasks, and depressive symptoms. The T2 young adult outcome measure included both objective and subjective indicators of productivity, social well-being, and autonomy in living situation. All malleable factors except social communication skills were significantly correlated with young adult outcomes. T1 executive functions, responsibility for daily tasks, and depressive symptoms jointly predicted 40.2% of the variance in young adult outcomes. Only depressive symptoms explained a significant amount of unique variance in young adult outcomes. In addition, depressive symptoms mediated the predictive association between executive functioning and young adult outcomes. The findings suggest that depressive symptoms may be a key intervention target for autistic high school students. Adapting cognitive behavioral approaches to comprehensively address multiple transdiagnostic factors such as executive functions, responsibility for daily tasks, and mental health may be a promising avenue to promote positive post-school outcomes in this population.