Background: The COVID-19 pandemic and the protection measures to contain its spread have massively changed daily lives of billions of children and adolescents worldwide. Objective: We conducted a systematic review to investigate the global longitudinal effects of the COVID-19 pandemic on various mental health outcomes in children and adolescents over a period of one and a half years. Methods: This review was conducted in accordance with the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The databases "PubMed", "Web of Science", and "APA PsycInfo" were searched (last access: 01/2022). Studies were included if they were peer-reviewed and published between December 2019 and December 2021, if they followed a longitudinal or repeated cross-sectional design, and if they assessed the effect of the COVID-19 pandemic or a related stressor on mental health indicators. Findings: Of 7,451 identified studies, 69 studies (n ~ 130,000) meeting eligibility criteria were included in a qualitative analysis. The results indicate a general trend of decreased psychological well-being, increased psychopathological distress, and heightened symptom levels (particularly of depressive and anxiety symptoms) from before to during the pandemic. Data suggests that both the intensity of protection measures and infection dynamic were positively associated with severity of psychopathology. The most reported influencing factors on the effect of the pandemic on child and adolescent mental health were age, gender, socio-economic status, previous state of mental and physical health, self-regulation abilities, parental mental health, parenting quality, family functioning, social support, isolation and loneliness, health-related worries, and consistent routines and structure. Conclusion: Our systematic review shows that children and adolescents worldwide have experienced increased psychological distress due to the COVID-19 pandemic. These results call for improvement in access to child and adolescent mental health care and the prioritisation of child and adolescent well-being in political decision making.