Representative school data on SARS-CoV-2 past-infection are scarce, and differences between pupils and staff remain ambiguous. We performed a nation-wide prospective seroprevalence study among pupils and staff over time and in relation to determinants of infection using Poisson regression and generalised estimating equations. A cluster random sample was selected with allocation by region and sociodemographic (SES) background. Surveys and saliva samples were collected in December 2020, March, and June 2021, and also in October and December 2021 for primary pupils. We recruited 885 primary and 569 secondary pupils and 799 staff in 84 schools. Cumulative seroprevalence (95% CI) among primary pupils increased from 11.0% (7.6; 15.9) at baseline to 60.4% (53.4; 68.3) in December 2021. Group estimates were similar at baseline; however, in June they were significantly higher among primary staff (38.9% (32.5; 46.4)) compared to pupils and secondary staff (24.2% (20.3; 28.8)). Infections were asymptomatic in 48–56% of pupils and 28% of staff. Seropositivity was associated with individual SES in pupils, and with school level, school SES and language network in staff in June. Associations with behavioural characteristics were inconsistent. Seroconversion rates increased two- to four-fold after self-reported high-risk contacts, especially with adults. Seroprevalence studies using non-invasive sampling can inform public health management.