Poor indoor air quality in scholar environments have been frequently reported, but its impact on respiratory health in schoolchildren has not been sufficiently explored. Thus, this study aimed to evaluate the associations between children's exposure to indoor air pollution (IAP) in nursery and primary schools and childhood asthma. Multivariate models (independent and multipollutant) quantified the associations of children's exposure with asthma-related health outcomes: reported active wheezing, reported and diagnosed asthma, and lung function (reduced FEV1/FVC and reduced FEV1). A microenvironmental modelling approach estimated individual inhaled exposure to major indoor air pollutants (CO2, CO, formaldehyde, NO2, O3, TVOC, PM2.5 and PM10) in nursery and primary schools from both urban and rural sites in northern Portugal. Questionnaires and medical tests (spirometry pre- and post-bronchodilator) were used to obtain information on health outcomes and to diagnose asthma following the newest international clinical guidelines. After testing children for aeroallergen sensitisation, multinomial models estimated the effect of exposure to particulate matter on asthma in sensitised individuals. The study population were 1530 children attending nursery and primary schools, respectively 648 pre-schoolers (3–5 years old) and 882 primary school children (6–10 years old). This study found no evidence of a significant association between IAP in nursery and primary schools and the prevalence of childhood asthma. However, reported active wheezing was associated with higher NO2, and reduced FEV1 was associated with higher O3 and PM2.5, despite NO2 and O3 in schools were always below the 200 μg m−3 threshold from WHO and National legislation, respectively. Moreover, sensitised children to common aeroallergens were more likely to have asthma during childhood when exposed to particulate matter in schools. These findings support the urgent need for mitigation measures to reduce IAP in schools, reducing its burden to children's health.