Primary Healthcare Physicians (PHCP) play an important role in early detection of Autism Spectrum Disorder (ASD). This study aims to assess the awareness of the PHCP of ASD early signs, identify the limiting factors affecting their knowledge, and discuss the preferred methods to fill in the knowledge gap. This cross-sectional study was conducted among 147 PHCP working in primary care centres and major hospitals in Riyadh, Saudi Arabia. The physicians were recruited through convenient sampling technique. A written questionnaire was used for data collection. The study findings revealed poor level of knowledge of ASD early signs among PHCP in Riyadh. A significant positive association was appreciated between the total mean knowledge score with both job title and experience years. Physicians who received prior psychiatry training were noted to have higher level of knowledge about ASD early signs. Since PHCP are first liners in receiving caregiver’s complaints, it is imperative to enhance their knowledge about ASD early signs to avoid delays in provision of acquired services to those children which adversely affects the health needs and quality of life of ASD children and their caregivers. Thus, it is recommended to provide specific training in ASD presentation and ASD screening tools.