Abstract Purpose Age-related macular degeneration (AMD), cataract, and glaucoma are leading causes of blindness worldwide. Previous genome-wide association studies (GWASs) have revealed a variety of susceptible loci associated with age-related ocular disorders, yet the genetic pleiotropy and causal genes across these diseases remain poorly understood. This study aims to identify genetic pleiotropic genes among AMD, cataract, and glaucoma. Methods We leveraged large-scale genetic and observational data from ocular disease GWASs and UK Biobank (UKBB) to investigate correlations among these ocular disorders. We undertook meta-analyses with the largest GWAS summary statistics of these ocular disorders to identify pleiotropic loci. We then comprehensively integrated eye-specific gene expression quantitative loci (eQTLs), epigenomic profiling, and 3D genome data to prioritize causal pleiotropic genes. Pathway enrichment analysis and drug repurposing analysis were also conducted. Results We found significant pairwise genetic correlations and consistent epidemiological associations among AMD, cataract, and glaucoma. Cross-disease meta-analysis uncovered seven pleiotropic loci, three of which were replicated in an additional cohort. Integration of variants in pleiotropic loci and multiple single-cell omics data identified that Müller cells and astrocytes were likely causal cell types underlying ocular comorbidity. After the integration with multi-omics data, 15 causal genes were identified. We found that pleiotropic genes were essential in nerve development and eye pigmentation, and targetable by existing drugs for the treatment of single ocular disorder. Conclusions These findings will not only facilitate the mechanistic research of ocular comorbidities but also benefit the therapeutic optimization of age-related ocular diseases.