In sub-Saharan countries, like South Africa, there is scant understanding of adolescent resilience to depression over time; the multisystemic resource combinations that support such resilience; and whether more diverse resource combinations yield better mental health dividends. In response, we conducted a longitudinal concurrent nested mixed methods study with 223 South African adolescents (mean age: 17.16 years, SD = 1.73; 64.60% girls; 81.60% Black). Using longitudinal mixture modeling, the quantitative study identified trajectories of depression and associations between trajectory membership and resource diversity. Using a draw-and-write methodology and reflexive thematic analyses, the qualitative study explored the resource diversity associated with each trajectory. Taken together, these studies identified four depression trajectories (Stable Low; Declining; Worsening; Chronic High) with varying resource diversity at baseline and over time. Resource diversity was inclusive of personal, relational, contextual, and culturally valued resources in both the Stable Low and Declining trajectories, with emphasis on relational supports. Personal resources were emphasized in the Worsening and Chronic High trajectories, and culturally valued and contextual resources de-emphasized. In summary, resource constellations characterized by within and across system diversity and cultural responsiveness are more protective and will be key to advancing sub-Saharan adolescent mental health.