The Canadian 24-hour movement behaviour (24-HMB) guidelines suggest that a limited amount of screen time use, an adequate level of physical activity (PA), and sufficient sleep duration are beneficial for ensuring and optimizing the health and quality of life (QoL) of children and adolescents. However, this topic has yet to be examined for children and adolescents with autism spectrum disorder (ASD) specifically. The aim of this cross-sectional observational study was to examine the associations between meeting 24-HMB guidelines and several QoL related indicators among a national sample of American children and adolescents with ASD. Significant associations were found between adhering to 24-HMB guidelines and selected QoL indicators. These findings highlight the importance of maintaining a healthy lifestyle as a key factor in promoting and preserving the QoL of children with ASD.