Background: Many children with Down syndrome do not undertake the recommended amount of daily physical activity. The aim of this study was to explore the barriers and facilitators to physical activity for this group. Methods: Eighteen in-depth interviews were conducted with 20 parents (16 mothers, 4 fathers) of children with Down syndrome aged between 2 and 17 years to examine what factors facilitate physical activity and what factors are barriers to activity for their children. The participants were recruited through a community disability organisation that advocates for people with Down syndrome and their families. Interviews were recorded, transcribed and independently coded and analysed by two researchers using thematic analysis. Results: Four themes on facilitators of physical activity were identified: (1) the positive role of the family; (2) opportunity for social interaction with peers; (3) structured accessible programmes that make adaptations for children with Down syndrome; and (4) children who were determined to succeed and physically skilled. Four themes on the barriers to physical activity were also identified: (1) characteristics commonly associated with Down syndrome; (2) competing family responsibilities; (3) reduced physical or behavioural skills; and (4) a lack of accessible programmes. Conclusions: The results highlight the important role of families in determining how much physical activity children with Down syndrome undertake and the effect that common characteristics associated with Down syndrome can have on maintaining an active lifestyle. Future research needs to concentrate on successful methods of encouraging physical activity, such as ensuring social interaction is part of the activity, and eliminating barriers to physical activity such as the a lack of appropriate programmes for children with Down syndrome. Implementing these strategies may encourage children with Down syndrome to participate more frequently in a physically active lifestyle.