Introduction: Longitudinal research examining the impact of coronavirus disease 2019 (COVID-19) school closures on the mental health of adolescents is scarce. Prolonged periods of physical and social isolation because of such restrictions may have impacted heavily on adolescents’ mental health and loneliness. Methods: The current study addresses a major gap by examining the impact of school closures on the mental health and loneliness of 785, 10- to 17-year-old Western Australian adolescents (mean age = 14.1, SD = 1.31), who were surveyed across four time points: twice before COVID-19, once as schools closed, and once post reopening of schools. Pre- and post-COVID-19 changes in mental health and loneliness were compared using linear mixed models. Random intercept cross-lagged panel models (RI-CLPMs) assessed temporal associations between loneliness, depression symptoms, and positive mental wellbeing. Results: Compared with pre-COVID-19 symptom levels, there were significant increases in depression symptoms, internalizing and externalizing symptoms, and a significant decrease in positive mental wellbeing at different points over time. Symptom change over time differed according to gender and pre-COVID-19 symptom severity. Significant increases in positive attitudes towards being alone and feelings of isolation occurred at different points over time. Gender differences were evident. RI-CLPMs highlighted the predictive significance of friendship quality and having a negative attitude towards being alone over time in relation to depression symptoms. A positive or negative attitude towards being alone was predictive of positive mental wellbeing over time. Conclusion: Findings provide evidence that COVID-19-related school closures adversely affected adolescents' mental health and feelings of loneliness.