Given the sharp increase in rates of depression during adolescence, especially in girls, it is important to identify which youth are at greatest risk across this critical developmental transition. During the present research, we examined whether (a) individual differences in cognition-emotion interaction, as reflected in cognitive control (CC) deficits and trait negative emotionality (NE), predict depression levels across a 1-year period (sixth-seventh grades); and (b) these temperamental traits create a particularly strong risk in girls. Youth (338 girls, 298 boys; M age in 6th grade = 11.96, SD = 0.37) reported on their trait NE and depressive symptoms; teachers reported on CC deficits. As hypothesized, compromised CC predicted subsequent depressive symptoms in girls with high, but not average or low, trait NE. This research informs efforts to identify which adolescents are at heightened risk for depression during the adolescent transition and points to possible candidates for early intervention.