The aim of this research was to evaluate the effects of social determinants (i.e., gender, educational vulnerability, and socioeconomic status) and resilience on the mental health of Chilean adolescents in pre-, during, and post-COVID-19 pandemic contexts. The study included a group of 684 students, ranging in age from 12 to 18 years, who were attending educational institutions in the city of Arica. The Child and Adolescent Assessment System (SENA) was used to measure mental health problems, the Brief Resilience Scale for Children and Youth (CYRM-12) was used to measure resilience, and the Vulnerability Index of Educational Institutions was used to measure educational vulnerability. The results suggest increases in depressive, anxious, and social anxiety symptomatologies over time (wave by year, 2018, 2020, and 2021). In addition, multiple linear regression models showed predictive effects of the COVID-19 pandemic, gender, vulnerability index, socioeconomic status, and resilient behaviors on mental health problems. The worsening of mental health indicators over time requires the greater coordination and integration of mental health experts in the most vulnerable educational centers.