To report the prevalence of depression, eating disorder symptoms, and impaired health-related quality of life (HRQOL) and examine their longitudinal associations with glycemia and diabetes complications in young adults with youth-onset type 2 diabetes. Participants recruited over a 4-year period were enrolled at 15 clinical diabetes centers in the follow-up observational Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) study. From 2014-2020, prevalence of symptoms of depression, eating disorders, and HRQOL by sex, race/ethnicity, and baseline family income were assessed annually. Longitudinal relationships between assessments of glycemia and complications with psychiatric symptoms and HRQOL were evaluated in adjusted models. Participants (n = 514) were 21.7 ± 2.5 years old with a diabetes duration of 8.6 ± 1.5 years in year 1 of TODAY 2 (2014). Symptoms of depression and impaired HRQOL were common and increased significantly over 6 years (14.0% to 19.2%, P = 0.003; and 13.1% to 16.7%, P = 0.009, respectively). Depression and impaired HRQOL were more common in women and those with lower baseline family income but did not differ by race/ethnicity. Rates of binge eating were stable over time; self-reported purging increased. Over time, symptoms of depression were associated with higher HbA1c, hypertension, and retinopathy progression; impaired HRQOL was associated with higher BMI, systolic blood pressure, hypertension, and retinopathy progression; and symptoms of eating disorders were associated with higher BMI. Significant psychiatric symptoms and impaired HRQOL are common among emerging adults with youth-onset type 2 diabetes and are positively associated with glycemia, hypertension, and retinopathy progression in this group that is at ongoing risk for medical morbidity.