The influence of perceived teacher support on trajectories of depression and self-esteem in middle school was examined using multigroup latent growth cross-domain models. A longitudinal sample of 2,585 students was followed from the sixth through the eighth grades. Students' perceptions of teacher support and general self-esteem declined and depressive symptoms increased over the course of middle school. We further found that, for both boys and girls, changes in perceptions of teachers' support reliably predicted changes in both self-esteem and depression. In particular, those students perceiving increasing teacher support showed corresponding decreases in depressive symptoms and increases in self-esteem. Gender differences were found for the initial levels of both perceptions of teacher support and general self-esteem. A competing model was also tested, which gave additional support for pathways of influence from perceptions of teacher support to depression and self-esteem, rather than the reverse. This study underscores the role of teacher support in facilitating students' adjustment to middle school and highlights the importance of using idiographic methodologies in the study of developmental processes. Implications and future directions are discussed.