This study aimed to provide a national estimate of the prevalence of the high risk of autism spectrum disorder (ASD) and their determinants. A national screening survey was conducted for 41,640 Egyptian children aged 1 to 12 years in two phases. Tools used were Vineland's Adaptive Behavior Scales, Modified Checklist for Autism in Toddlers, Gilliam Autism Rating scale, and Denver II Developmental screening test. The overall prevalence of children at high risk of ASD was 3.3% (95% CI:3.1%–3.5%). Children living without mothers in homes, suffered from convulsions (AOR = 3.67; 95%CI:2.8–4.8), a history of cyanosis after birth (AOR = 1.87; 95% CI:1.35–2.59) or history of LBW babies (AOR = 1.53; 95% CI:1.23–1.89) carried higher odds of being at high risk of ASD.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-023-04977-5.