Background Lateness in the diagnosis of autism spectrum disorders (ASD) results in significant disability and pressure on affected children and their families. We aimed to detect the preschool children who have high-risk criteria for ASD in Sharkia Governorate in Egypt and assess the prevalence and risk factors of ASD. A cross-sectional community-based study was done in 39 kindergartens throughout Sharkia Governorate, Egypt, using a multi-stage random sampling technique. The study included two phases, the screening phase, where 3722 preschool children were screened by Modified Check List for Toddlers/Revised (M-CHAT-R), and the diagnostic phase where the diagnosis of ASD among the high-risk children was made according to the research diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) of ASD administrated by experienced psychiatrists and the Childhood Autism Rating Scale (CARS). Results This study showed that 2.8% of children were at high risk for ASD. The prevalence of ASD in Sharkia Governorate was 5.4/1000. The significant risk factors for the disorder were the presence of factories near the house, first and middle child order, congenital anomalies, child medication during the first year of life, child chronic medical condition, child attachment to TV, a medical condition affecting mother during pregnancy, and psychiatric disorders history in the family. Conclusion Autism spectrum disorder is prevalent in preschool children in Sharkia, Egypt, and multiple risk factors contribute to this prevalence.