Drug use and depression co-occur and disproportionately affect Latinx sexual minority youth relative to their heterosexual Latinx peers. However, heterogeneity in co-occurring patterns of drug use and depressive symptoms is unknown. The objective of the current study was to identify patterns of drug use and depressive symptom trajectories and examine how these patterns varied between Latinx sexual minority youth and Latinx non-sexual minority youth. Latent class trajectory analysis identified distinct patterns of drug use and depressive symptom trajectories among 231 Latinx adolescents (Latinx sexual minority youth:n= 46, 21.4%; Latinx non-sexual minority youth:n= 169, 78.6%). After identifying class mean trajectories, we examined differences in mean trajectories across groups. A 3-class model was selected as the optimal class trajectory model for both groups, yet classes and trajectories differed. There were differences in initial levels of depression and drug use trajectories between both groups, as well as differences in patterns of drug use trajectories between both groups in two of the three classes. Given the variation in trajectory patterns, there is a need for practitioners to consider the unique needs of both groups to inform the development of preventive interventions for these two populations.