Objective: Classroom-based active breaks can help typically developing children to reduce prolonged sitting time, increase physical activity, and improve cognitive functions and on-task behavior. Yet, this approach has not been tested in children with intellectual disability, although this population are insufficiently active and at a higher risk of obesity compared to typically developing children. Hence, this study aimed to test the effects of a 5-week active break intervention on cognitive functions, sedentary patterns, and on-task behavior in schoolchildren with intellectual disability. Method: We recruited twenty-four children, aged between 8 and 12 years (37.5% girls), from two schools. Children’s cognitive functions (response inhibition, lapses of attention, interference and working memory) were measured at baseline and trial end using computer-based tests. Sitting, standing and movement patterns were assessed with inclinometers during class/school periods, at baseline, mid-trial, and end of trial. On-task behavior was directly observed in the classroom, before and after active breaks. Linear mixed models were used to investigate the intervention effects on cognitive functions and sedentary patterns. Generalised linear mixed models were used to analyse on-task behaviour data. Teachers’ experience was captured using one-on-one interviews. Results: A significant time × group interaction was found for working memory favouring the intervention group (B = 11.56, 95% confidence interval [1.92, 21.21]). No significant effects were found in relation to the other measures of children’s cognition or on-task behaviour. Relative to the control group, the intervention group showed significant positive changes in stepping time (+25 min) and step count (+1913 steps), and significant negative changes in time spent in sitting bouts greater than 5 mins (–60 mins) or greater than 20 min (–73 mins) from baseline to mid-trial; similar significant differences were also noted by the end of trial. Teachers indicated that active breaks are feasible to implement, although adaptations may be needed to cater for children’s specific needs. Discussion: Classroom-based active breaks are feasible to implement in the real school environment and can contribute to increase physical activity and reduce sedentary behaviour in children with intellectual disability and might also benefit their working memory. This study is the first to have tested the effects of classroom-based active breaks in this population. Further research is required to clarify the effects on cognitive functions and whether this strategy has other benefits in children with intellectual disability. Conflict of interest statement: J.S. declares that she has a potential conflict of interest as her husband established a business to manufacture height-adjustable desks for schools in 2017. However, she was not involved in the data analysis. N.R. currently receives funding from the Moose Foundation, Victorian Department of Education and Training, MECCA Brands, Wenig Family, Geelong Community Foundation, and Grace and Emilio Foundation to conduct research in the field of neurodevelopmental disorders and inclusion. N.R. also receives funding from the Ferrero Group Australia as part of its Kinder + Sport pillar of Corporate Social Responsibility initiatives to promote active lifestyles among young people. N.R. has previously received donations from Vic Health and Bus Association Victoria; and previous speaker honorarium from Novartis (2002), Pfizer (2006) and Nutricia (2007); and is a Director of the Amaze Board (Autism Victoria). N.R. has also received funding from the Australian National Disability Insurance Agency. None of the companies or organisational bodies listed above had a role in this research including the data collection and analysis, and/or the interpretation of results; in writing of this abstract or the manuscript; and/or in the decision to submit the article for publication. The other authors declare no conflicts of interest. This research was funded by the Department of Education and Training, State Government of Victoria. The funders had no role in the design of the study; in the data collection and analyses, and/or the interpretation of data; in the writing of the abstract/manuscript, or in the decision to publish the results.