Spontaneous osteonecrosis of the knee (SONK) is a common disease in elderly humans. Clinically, SONK presents with the sudden onset of severe knee joint pain, usually in the load-bearing area of the medial compartment of the knee. Articular cartilage lesions are secondary to subchondral trabecular bone necrosis. These biochemical and structural changes in the bone and cartilage alter the biomechanics of the joint, which may then lead to secondary osteoarthritis and ultimately joint destruction. We observed 3 cases of osteonecrosis affecting the knee joint of free-ranging Macaca mulatta (rhesus macaques). The histopathology of these cases consists of defects in the subchondral bone with articular cartilage necrosis and repair. The defects were associated histologically with secondary osteoarthritis in 2 cases. The osteonecrotic lesions in the macaques resemble closely spontaneous osteonecrosis of the knee as seen in humans. This is the first report of spontaneous osteonecrosis of the knee in nonhuman primates.