Background: Depression-literacy, which is the foundational requirement for symptom recognition, positive attitude and help-seeking, is poor among adolescents in Nigeria. This study, therefore, aims to determine the impact of a school-based training program on depression-literacy among a cohort of high-school students and their teachers in South-West Nigeria. Methods: An adapted version of the Break Free from Depression, a 4-module depression awareness curriculum for staff and students, was implemented among students and their teachers. Paired-sample T-test was used to assess the domain-specific (knowledge, attitude, and confidence) impact of the training by comparing the baseline and immediate (within the week of the training) post-scores. Results: A total of 3,098 students and 294 teachers from 21 schools across three states in South-West Nigeria successfully completed the training. There was a significant positive difference (p<.05), at post-test, in the knowledge, attitude, and confidence among the students. The same was observed among teachers except for attitude where positive change did not reach significant level (p=.06). When statistically significant, the calculated effect size (eta squared) was highest for knowledge (students: .07, p=.001; teachers: .08, p<.000) and least for attitude (students: .003, p=.002 teachers: .085, p=.06). Multiple regression analyses result showed that the level of pre-scores predicted the magnitude of change in all domains of depression-literacy (p<.05) after controlling for age, gender, and type of school among the students, but not for teachers. Conclusions: School-based depression-literacy programs can lead to significant positive change in knowledge, attitude, and confidence of students and teachers.