Deficits in social communication, restricted interests, and repetitive behaviours are hallmarks of autism spectrum disorder (ASD). Despite high genetic heritability, the majority of clinically diagnosed ASD cases have unknown genetic origins. We performed genome sequencing on mothers, fathers, and affected individuals from 104 families with ASD in Oman, a Middle Eastern country underrepresented in international genetic studies. This approach identified 48 novel candidate genes significantly associated with ASD in Oman. In particular, 35 of these genes have been previously implicated in neurodevelopmental disorders (NDDs) in other populations, underscoring the conserved genetic basis of ASD across ethnicities. Genetic variants within these candidate genes that would impact the encoded protein included 1 insertion, 4 frameshift, 6 splicing, 12 nonsense, and 67 missense changes. Notably, 61% of the SNVs were homozygous, suggesting a prominent recessive genetic architecture for ASD in this unique population. The scarcity of genetic studies on ASD in the Arabian Peninsula has impeded the understanding of the unique genetic landscape of ASD in this region. These findings help bridge this knowledge gap and provide valuable insights into the complex genetic basis of ASD in Oman.