BACKGROUND: Sugar-sweetened beverages (SSBs) are the primary source of dietary added sugars in children, with high consumption commonly observed in more deprived areas where obesity prevalence is also highest. Associations between SSB consumption and obesity in children have been widely reported. In March 2016, a two-tier soft drinks industry levy (SDIL) on drinks manufacturers to encourage reformulation of SSBs in the United Kingdom was announced and then implemented in April 2018. We examined trajectories in the prevalence of obesity at ages 4 to 5 years and 10 to 11 years, 19 months after the implementation of SDIL, overall and by sex and deprivation. METHODS AND FINDINGS: Data were from the National Child Measurement Programme and included annual repeat cross-sectional measurement of over 1 million children in reception (4 to 5 years old) and year 6 (10 to 11 years old) in state-maintained English primary schools. Interrupted time series (ITS) analysis of monthly obesity prevalence data from September 2013 to November 2019 was used to estimate absolute and relative changes in obesity prevalence compared to a counterfactual (adjusted for temporal variations in obesity prevalence) estimated from the trend prior to SDIL announcement. Differences between observed and counterfactual estimates were examined in November 2019 by age (reception or year 6) and additionally by sex and deprivation quintile. In year 6 girls, there was an overall absolute reduction in obesity prevalence (defined as >95th centile on the UK90 growth charts) of 1.6 percentage points (PPs) (95% confidence interval (CI): 1.1, 2.1), with greatest reductions in the two most deprived quintiles (e.g., there was an absolute reduction of 2.4 PP (95% CI: 1.6, 3.2) in prevalence of obesity in the most deprived quintile). In year 6 boys, there was no change in obesity prevalence, except in the least deprived quintile where there was a 1.6-PP (95% CI: 0.7, 2.5) absolute increase. In reception children, relative to the counterfactual, there were no overall changes in obesity prevalence in boys (0.5 PP (95% CI: 1.0, -0.1)) or girls (0.2 PP (95% CI: 0.8, -0.3)). This study is limited by use of index of multiple deprivation of the school attended to assess individual socioeconomic disadvantage. ITS analyses are vulnerable to unidentified cointerventions and time-varying confounding, neither of which we can rule out. CONCLUSIONS: Our results suggest that the SDIL was associated with decreased prevalence of obesity in year 6 girls, with the greatest differences in those living in the most deprived areas. Additional strategies beyond SSB taxation will be needed to reduce obesity prevalence overall, and particularly in older boys and younger children. TRIAL REGISTRATION: ISRCTN18042742.