Youth in foster care disproportionately receive special education services and those in foster care and special education are at compounded disadvantage as they attempt to transition from high school to adult life. Given enhanced self-determination has been associated with improved transition outcomes for youth in special education, the purpose of this longitudinal, randomized trial was to evaluate the efficacy of the TAKE CHARGE self-determination intervention for improving the transition outcomes of those highly at-risk youth who are in both foster care and special education. The intervention included coaching for youth in the application of self-determination skills to achieve youth-identified goals, and youth participation in mentoring workshops with near peer foster care alumni. Sixty-nine youth, ages 16.5 to 17.5, were randomly assigned to TAKE CHARGE or to the foster care independent living program. Assessment at baseline, post-intervention and at one year follow-up revealed moderate to large effect sizes at post-intervention and one year follow-up for the differences between groups in self-determination, quality of life, and utilization of community transition services. Youth in the intervention group also completed high school, were employed, and carried out independent living activities at notably higher rates than the comparison group. Self-determination was confirmed as a partial mediator of enhanced quality of life. Implications of the findings for supporting youth in foster care, with and without disabilities, as well as future research directions are discussed.