An integrated approach combining whole exome sequencing (WES) and autozygosity mapping was used to molecularly diagnose inherited retinal disease (IRD) in 192 unrelated Iranian families, 76.1% of which originate from a consanguineous background. Data analysis was performed using an in-house pipeline to detect single-nucleotide variants (SNVs), small insertions and deletions, copy number variants (CNVs) and runs of homozygosity (ROHs). Using this approach, we obtained a molecular diagnosis for 72.9% of the cohort. In total, 209 variants were identified in 78 IRD-associated genes. The majority occurred only once (81.8%) and 52.9% were novel. Variants in ROHs were found in 82.8% of patients from consanguineous backgrounds. The importance of structural variation (SV) was demonstrated, with CNVs identified in 5.3%, including several novel CNVs. Multilocus genomic variation was observed in two families. This integrated study using WES and in-depth variant assessment significantly expanded the molecular spectrum of IRD in Iran, an understudied population.