There is evidence that depression during adolescence and early adulthood is marked by deficits in interpersonal functioning. However, few studies have prospectively examined whether interpersonal difficulties are a risk factor for depression onset, so it is unclear whether these deficits in interpersonal functioning are products or predictors of depression. The present study aimed to clarify the direction of association between interpersonal factors and depression by examining whether social factors longitudinally predicted onset of depression in a diverse sample of young women with no history of depression. Hierarchical multiple regression analyses controlling for baseline depressive symptoms indicated that poorer family relationship quality and anxious attachment cognitions predicted onset of depressive episodes during the 2-year period. Further, a wide variety of interpersonal factors predicted depressive symptoms over 6 months, including poor peer and family relationship quality, difficulty being close to others, and difficulty depending on others, controlling for baseline depressive symptoms and college attendance. The results provide evidence for the importance of an interpersonal perspective on vulnerability to depression.