We examined rural-urban differences in emergency department visits, and child and clinical characteristics associated with visits for U.S. children aged 3-17 years with autism spectrum disorder (ASD). Rural children with ASD were twice more likely to have emergency department visits in urban hospitals than rural children without ASD. The children with ASD in rural areas were economically disadvantaged and concentrated in the South and Midwest regions. Rural children diagnosed with ASD and multiple comorbidities during emergency department visits were 1.6 times as that of urban children. Rural children with ASD, particularly those with multiple comorbidities, require more emergency department services when compared with urban children with ASD.