Background Ophthalmic lesions comprise a wide range of disorders ranging from benign and precancerous to malignant lesions. This study was undertaken to investigate the prevalence and clinicopathological relations of ophthalmic lesions in Jimma University Medical Center as characterization of these lesions has vital importance for better diagnosis and management of patients. Methods A retrospective study of 209 ophthalmic lesions in Jimma university medical center from 2016 to 2020 which were registered on the biopsy log book was included in the study. Data were entered and cleaned Using an excel spreadsheet and analyzed in SPSS version 26. Descriptive statistics and regression analysis were done to determine the proportion of the ophthalmic lesions. Results 209 cases of ophthalmic lesions were reviewed, of these 118 (56.5%) were malignant and 58 (27.8%) were benign lesions and CIN accounted for 20 (9.6%). Non-neoplastic lesions had the lowest group of cases observed accounting for 8 (3.8%). Conjunctiva was the most common site of ophthalmic lesions 128 (61.2%). Squamous cell carcinoma was the leading ophthalmic malignancy 58 (49.1%). There was a bimodal distribution of age, in the first decade due to retinoblastoma and the fourth decade due to Squamous cell carcinoma. Male to female ratio was found to be 1.7:1. The second decade and third decades of life had an 87% and 85% decrease in the odds of developing malignancy, with a p-value of 0.006 (AOR: 0.12 (CI: 0.02–0.54) and p-value of 0.007 (AOR: 0.14(CI: 0.03–0.58) respectively. Intra-ocular lesions were 22 times more likely to be diagnosed with a malignant diagnosis than other anatomical sites with a p-value of 0.026 (AOR: 22.05, CI: 2.54–9.84). Conclusion The commonest ophthalmic malignancy was Squamous cell carcinoma. There was a bimodal distribution of age, in the first decade due to retinoblastoma and the fourth decade due to squamous cell carcinoma. The second and third decades of life had decreased odds of being diagnosed with ophthalmic malignancy. The intra-ocular location of tumors was associated with increased odds of ophthalmic malignancy.