Previous research has demonstrated that people who report same-sex experience tend to have poorer mental health than heterosexual people in adolescence and adulthood. Yet, little is known about how same-sex experience is associated with changes in mental health between the two life stages. Using data from the National Longitudinal Study of Adolescent Health (n = 12,056), this study assesses patterns of same-sex experience between adolescence and young adulthood and their consequences for changes in depressive symptoms, binge drinking, and drug use. Compared to people with no same-sex experience, those who report such experience only in adolescence show greater levels of mental health problems in adolescence, but they do not show any worse mental health changes during the transition into young adulthood. People who develop their first same-sex experience in young adulthood, however, tend to show worse changes, consistent with the argument that entry into a stigmatized role is psychologically harmful. Among females, those who report same-sex experience in both life stages also show worse mental health changes, indicating that the continuity in minority status contributes to their cumulative disadvantage. However, these differences are modest, and substantial amounts of variations in mental health changes are observed within each group. Findings are used to address the dynamic aspect of mental health disparity linked to sexuality.