Few multinational studies have assessed risk factors and coping strategies associated with the impact of the COVID-19 pandemic on children’s mental health over time. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is the largest transcontinental, multi-wave, cross-sectional survey collecting multi-nation data on well-being and psychopathology during the pandemic. We analyzed country-specific, general-population-based, representative COH-FIT data of 6067 children aged 6–13 years from 12 countries across repeated cross-sectional waves over a period of >2 years (Apr/2020–May/2022), addressing through current and retrospective assessment pre- to intra-pandemic changes in well-being (WHO-5) and general psychopathology scores (P_c) (0–100) in relation to COVID-related deaths, stringency index, eight a priori risk factors, and 16 coping strategies in different responders at each wave. From pre- to intra-pandemic, WHO-5 scores decreased (−4.59, 95 %CI=−6.18 to −2.99, p < 0.001), while PC-scores increased (+6.68, 95 %CI=4.48–8.88, p < 0.001) significantly, following distinct time patterns but both returning to near pre-pandemic levels. Changes in both scores varied by country. WHO-5 scores correlated strongly with P_C and subdomain scores. Both score changes were significantly but minimally associated to COVID-19 deaths/stringency index. The proportion of children screening positive for depression increased from 3.9 % to 8.3 % (χ²=145.70, p < 0.001) and for major depression from 0.6 % to 2.2 % (χ²=68.64, p < 0.001) intrapandemic. WHO-5 and P_C-score changes were significantly associated with female gender, school closure, and pre-existing physical and mental conditions, with cumulative effects. The five most frequently endorsed coping strategies were family contact (85.2 %), friends (67.3 %), outdoor play (54.0 %), pet interaction (51.5 %), and internet use (50.9 %). Identified risk groups and coping strategies can inform targeted interventions and global public health policy. Trial Registration: ClinicalTrials.gov;