This report documents the progression of chronic lymphocytic leukemia into diffuse aggressive lymphoma, or Richter’s syndrome, first manifesting as unilateral ophthalmic disease in a 10-year-old coonhound. Following a 1.5-year course of chronic leukemia that was in a clinical remission, the dog was presented for a protruded left globe. Orbital ultrasound revealed a vascular mass located ventromedially and causing indentation of the sclera. Skull computed tomography showed exophthalmos due to a soft tissue mass and concurrent left mandibular bony lysis. Abdominal ultrasound and computed tomography revealed a large right adrenal mass, peritoneal lymphadenopathy, multiple liver nodules, kidney infarcts, and dorsal body wall nodules. A diagnosis of uveal lymphoma with scleral extension was obtained on histopathology after surgical removal of the affected eye. Cancerous cells were large with high-grade proliferative features, consistent with T-cell lymphoma based on immunophenotyping (CD3+/CD20-). The dog was euthanized 2 days postoperatively due to declining systemic condition. Richter’s syndrome is a rare condition, but generally carries a grave prognosis. To the authors’ knowledge, this is the first report of Richter’s syndrome in a veterinary patient presenting with an ophthalmic manifestation.