© 2015, Springer Science+Business Media New York. Background and Objectives Previous literature using small sample sizes and limited geographic areas report that overweight/obesity and physical inactivity occur at higher rates among children with autism spectrum disorder (ASD) compared to typically developing peers. The purpose of this study was to examine obesity, overweight, physical activity, and sedentary behavior among children and youth with and without ASD using nationally representative data and controlling for secondary conditions, including intellectual and learning disabilities, ADHD, developmental delay, and other mental, physical, and medical conditions, as well as medication use. Methods Data were collected from the 2011–2012 National Survey of Children’s Health, a cross-sectional survey of 65,680 (weighted N = 49,586,134) children aged 6–17 (1385 with ASD, weighted N = 986,352). Logistic regression was used to estimate odds ratios, adjusting for demographics and possible secondary conditions. Results Having a diagnosis of ASD was associated with higher odds of obesity (OR 1.76, CI 1.27–2.43; p = <0.001). However, after additional adjustment for possible secondary conditions, ASD diagnosis was no longer associated with obesity. Those with moderate ASD (OR 0.58, CI 0.36–0.93; p = <0.05) reported lower odds of sedentary behavior, but this association failed to achieve significance after adjustment for secondary conditions and medication use. No significant associations between ASD and overweight or physical activity were found. Conclusions These findings suggest that ASD diagnosis is not significantly associated with obesity status after adjustment for possible secondary conditions and medication use. Decision makers, clinicians, and researchers developing interventions for children with ASDs should consider how secondary conditions may impact obesity and related activities.