It is unclear whether children with Down syndrome have differing physical activity and sedentary behavior levels compared to typical children. This study addressed this evidence gap in a national sample. Physical activity/sedentary behavior were ascertained by parental report. Findings highlighted that children with Down syndrome were less likely to engage in regular physical activity compared to typical children and had the lowest likelihood of regular physical activity among all subgroups with developmental disabilities/special healthcare needs. Children with Down syndrome were also more likely to watch high volumes of television compared to typical children, although this was nonsignificant upon adjustment for general health. It was concluded that children with Down syndrome are in urgent need for interventions/programs that promote physical activity.