Depression is a major public health problem among adolescents and preadolescents in the United States. Clinical scientists have spent considerable resources designing and testing depression interventions. Some programs can prevent and reduce depression to a modest degree,¹ while others show null or potentially adverse impacts on youth mental health.² However, due to low access to treatment for depression (more than 50% of adolescents with depression symptoms never access treatment at all³) and the heterogeneity of depressive symptoms, no interventions have led to meaningful declines in the overall burdens of depression for adolescents.⁴ In high school students, rates of self-reported persistent feelings of sadness or hopelessness and suicidal thoughts and behaviors increased between 2011 and 2021 in the United States.⁵ Status quo approaches are unlikely to sustainably improve adolescent depression. We propose that a critical and often overlooked contributor to this shortfall is youth autonomy—a key, developmentally aligned need for adolescents—to reduce rates of depression at the population level. During adolescence, individuals begin to separate from their parents, guardians, and caregivers (hereafter caregivers) and make decisions independently. This process is critical for healthy identity formation, self-efficacy, and mental health, including prevention and reduction of depression.⁶ Youth autonomy is among myriad multilevel factors (eg, social connectedness, food and housing insecurity, adversity exposure) relevant to depression trajectories. However, in contrast to many social and structural contributors to depression, perceived autonomy of youths is relatively modifiable through individual-level intervention, making it a promising intervention target. The psychosocial importance of youth autonomy stands in sharp contrast to modern policies and structures that undermine youth independence and control—including within many existing depression interventions.