Background: Concerns have been raised over teachers' mental health literacy in low-income countries and lower- and middle-income countries wherein pediatric mental health resources are limited. This study aims to investigate adolescent depression literacy among teachers in Eswatini and to explore the role of urbanicity. Methods: We conducted a cross-sectional survey in 59 public high schools in Eswatini in 2019-2020. Data were collected by a paper-and-pencil questionnaire; depression literacy was assessed by the 17-item Adolescent Depression Knowledge Questionnaire. Results: Teachers' adolescent depression literacy item-level correct rates fell between 27 and 80%. Although the multivariate response models indicated that teaching in urban areas was slightly associated with having higher depression literacy in general (adjusted odds ratio [aOR] = 1.46; 95% confidence interval = 1.00-2.12), such urban-rural differences did not manifest homogeneously across all items: urban teaching was significantly linked with reduced correct responses toward certain items concerning depression etiology and treatment, including "depression runs in some families," "major stress as a necessary cause," and "a curable illness" (aOR = 0.57 [approximately] 0.68). Conclusion: Urban-rural differences in teachers' depression literacy were manifested at both scale- and item-levels. A critical need exists for urban/rural areas-tailored intervention on teachers' literacy toward mental disorders in the resource-limited regions to better improve health and developmental outcomes of students.