The COVID-19 pandemic has led to extensive and unprecedented periods of school closures across the world, causing students to engage in learning remotely. The current study aimed to (a) explore adolescents’ experiences of remote learning during the COVID-19 pandemic, (b) identify psychosocial factors associated with school-related stressors, and (c) examine the relationship between adolescents’ perceived school-related stressors and mental health difficulties during the pandemic. A sub-study of the Australian 18-year longitudinal Mothers’ and Young People’s Study was conducted during the COVID-19 pandemic between July and September 2020. A total of 264 adolescents (aged 14–17 years) and their mothers completed an online survey about remote learning, psychosocial stressors, and their mental health during the pandemic. Four in five adolescents reported school-related stressors during the pandemic, with the majority feeling overwhelmed and in need of more support from teachers. Factors associated with adolescents’ perceptions of school-related stressors included financial hardship, stress in the family home (conflict and crowdedness), and few protective or resilience factors. Adolescents experiencing school related stressors were more likely to report depressive and anxiety symptoms. Adolescents with co-occurring family stress perceived more school-related stressors, reinforcing the notion that children experiencing social and economic disadvantage were disproportionately affected by school closures during the pandemic. These findings underscore the need to investigate the long-term impacts of school closures during the pandemic on adolescents’ academic and mental health outcomes.