This three-wave prospective study investigated the reciprocal relationships among school-related stress, school-related social support, and distress in a cohort of 767 secondary school students (mean age 13.9 years). Stress, support, and distress were measured at three occasions with six-month lags between. Reciprocal relationships were analyzed with multivariate multilevel modeling (MLwiN). Each of the three factors at baseline predicted change in one or two of the other factors at subsequent measurements, indicating a complex pattern of reciprocal relationships among stress, support, and distress across time. A high level of distress at baseline predicted a lower level of support and a higher level of stress six months later. High levels of stress at baseline predicted a higher level of distress and a lower level of support 12 months later. The results are consistent with a transactional and dynamic model of stress, support, and distress, and indicate the need to view school-related stress, support, and distress as mutually dependent factors.