OBJECTIVES: To assess socioeconomic and geographical factors associated with COVID-19 vaccine uptake in pupils attending state-funded secondary schools in England. DESIGN: Cross-sectional observational study. SETTING: State-funded schools in England. PARTICIPANTS: Pupils aged 12-17 years attending state-funded schools in England for the academic year 2021/2022. OUTCOME MEASURES: Demographic, socioeconomic and geographical factors associated with vaccination uptake. We linked individual-level data from the English Schools Census to the National Immunisation Management System to obtain COVID-19 vaccination status of 3.2 million adolescents. We used multivariable logistic regression to assess demographic, socioeconomic and geographical factors associated with vaccination. RESULTS: By 9 January 2022, 56.8% of adolescents aged 12-17 years old had received at least one dose, with uptake increasing from 48.7% in those aged 12 years old to 77.2% in those aged 17 years old. Among adolescents aged 12-15 years old, there were large variations in vaccine uptake by region and ethnic group. Pupils who spoke English as an additional language (38.2% vs 55.5%), with special educational needs (48.1% vs 53.5%), eligible for free school meals (35.9% vs 58.9%) and lived in more deprived areas (36.1% in most deprived vs 70.3% in least deprived) had lower vaccine uptake. Socioeconomic variables had greater impact on the odds of being vaccinated than geographical variables. School-level analysis found wide variation in vaccine uptake between schools even within the same region. Schools with higher proportions of pupils eligible for free school meals had lower vaccine uptake. CONCLUSIONS: We found large differences in vaccine uptake by geographical region and ethnicity. Socioeconomic variables had a greater impact on the odds of being vaccinated than geographical variables. Further research is required to identify evidence-based interventions to improve vaccine uptake in adolescents.