This study aimed to test the effectiveness of the Whole of Systems Trial of Prevention Strategies for Childhood Obesity (WHO STOPS Childhood Obesity) for behavioral, health-related quality of life (HRQoL), and BMI outcomes. Methods: This was a cluster randomized trial of 10 communities randomly allocated (1:1) to start intervention in 2015 (step 1) or in 2019 (after 4 years) in South West Victoria, Australia. Data were collected from participating primary schools in April to June of 2015 (73% school participation rate), 2017 (69%), and 2019 (63%). Student participation rates were 80% in 2015 (1,792/2,516 invited), 81% in 2017 (2,411/2,963), and 79% in 2019 (2,177/2,720). Repeat cross-sectional analyses of measured height and weight (grades two, four, and six [aged approximately 7 to 12 years]), self-reported behavior, and HRQoL (grades four and six) were conducted. Results: There was an intervention by time interaction in BMI z scores (P = 0.031) and obesity/overweight prevalence (P = 0.006). BMI z score and overweight/obesity prevalence decreased between 2015 and 2017 and increased between 2017 and 2019 in intervention communities. The intervention significantly reduced takeaway food consumption (P = 0.034) and improved physical (P = 0.019), psychosocial (P = 0.026), and global (P = 0.012) HRQoL. Water consumption increased among girls (P = 0.033) in the intervention communities, as did energy-dense, nutrient-poor snack consumption among boys (P = 0.006). Conclusions: WHO STOPS had a positive impact on takeaway food intake and HRQoL.