Guided by ecodevelopmental theories, the present study examined how both culture-specific and general risk and protective factors across contexts predicted trajectories of Latinx youth’s internalizing symptoms during early and middle adolescence. Participants included 547 Latinx youth (M age = 12.80; 55% females) recruited in middle school and followed prospectively across four time points spanning two years. Youth reported on their internalizing symptoms at all four time points, and risk and protective factors were measured at Time 1 (T1). Latent class growth curve modeling was used to examine heterogenous trajectories of change in internalizing symptoms separately for females and males, and risk and protective factors were examined as predictors of class membership. Three classes based on symptom trajectories emerged for both females and males, with most adolescents falling into classes characterized by low symptoms that remained stable or decreased over time. Risk and protective factors were predictive of class membership in theoretically meaningful ways. Some predictors of internalizing symptom trajectories differed between females and males. Findings inform our understanding of factors that influence developmental trajectories in Latinx youth and can contribute to the refinement of prevention and intervention efforts to help ensure the well-being of this population.