Objectives: To examine whether meeting vs not meeting movement/non-movement guidelines (moderate-to-vigorous physical activity [MVPA], screen time, sleep duration), and combinations of these recommendations, are associated with health-related quality of life (HRQoL) in children from 12 countries in five major geographic regions of the world and explore whether the associations vary by study site. Study design: Observational, multinational cross-sectional study. Methods: This study included 6106 children aged 9e11 years from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Participants completed the KIDSCREEN-10 to provide a global measure of their HRQoL. Sleep duration and MVPA were assessed using 24-h accelerometry. Screen time was assessed through self-report. Meeting the recommendations was defined as 60 min/day for MVPA, 2 h/day for screen time, and between 9 and 11 h/night for sleep duration. Age, sex, highest parental education, unhealthy diet pattern score, and body mass index z-score were included as covariates in statistical models. Results: In the full sample, children meeting the screen time recommendation, the screen time þ sleep recommendation, and all three recommendations had significantly better HRQoL than children not meeting any of these guidelines. Differences in HRQoL scores between sites were also found within combinations of movement/non-movement behaviors. For example, while children in Australia, Canada, and USA self-reported better HRQoL when meeting all three recommendations, children in Kenya and Portugal reported significantly lower HRQoL when meeting all three recommendations (relative to not meeting any). Conclusions: Self-reported HRQoL is generally higher when children meet established movement/non-movement recommendations. However, differences between study sites also suggest that interventions aimed at improving lifestyle behaviors and HRQoL should be locally and culturally adapted.