CNS lymphoma is a rare form of non-Hodgkin lymphoma that primarily affects the brain, spinal cord, leptomeninges, or eyes, leading to severe neurological or ophthalmological complications. This case report details a 44-year-old male with human immunodeficiency virus and diffuse large B-cell lymphoma who experienced permanent vision loss due to optic perineuritis, a rare presenting symptom indicative of underlying CNS involvement. Despite previous remission, imaging revealed focal enhancements suggesting CNS lymphoma, highlighting diagnostic and management challenges in relapsed lymphoma, especially in immunocompromised patients. The patient's rapid symptom onset and subsequent irreversible vision loss emphasize the need for early detection and intervention. Despite aggressive treatment with systemic and intrathecal chemotherapy, the patient's visual function did not recover. This case highlights the importance of monitoring high-risk lymphoma patients for CNS relapse by way of regular neuroimaging to facilitate prompt diagnosis and treatment of optic nerve involvement, thereby mitigating the risk of irreversible neurological damage. Future research should focus on optimizing management strategies for CNS lymphoma and improving outcomes for patients with such rare and debilitating complications.