Objective To study changes in biomechanical characteristics of the femoral head during the progression of avascular osteonecrosis and investigate the mechanism of these biomechanical changes. Methods Twenty-four three-foot weight bearing canine models with osteonecrosis of the femoral head (ONFH) were established by fixing one fore limb of the canine. Osteonecrosis was induced in all experimental animals by randomly injecting 5 mL pure ethanol into one side of the femoral head, and the contralateral femoral head was injected with an equal amount of normal saline as the control group. The canines were killed at 1st, 3rd, 6th, and 12th week after the injection of ethanol, with six canines in each group. The radiographic, histological changes and biomechanical characteristics of the femoral head were observed and analyzed. Results At 3rd week, 29% reduction of indentation stiffness and 32.9% reduction of elastic modulus in the cancellous bone were found in the infected femoral heads compared to the control heads, and a low density area was detected only in MRI and osteonecrosis was the main histological characteristics. At 6th and 12th week, the indentation stiffness in the infected femoral heads was reduced by 45.5% and 48.7%, respectively, and the elastic modulus of the cancellous bone in the infected femoral heads was reduced by 34.1% and 32.4%, respectively, compared to the control heads. At 6th week, uneven bone density of the femoral head was detected in radiographs, and the progression of osteonecrosis and bone healing was found at the same time. At 12th week, areas of reduced bone mineral density beneath the load bearing position of the femoral head were observed on radiographs. Collapse of the articular cartilage surface and narrowing of the joint space were the main histological findings. Conclusions Biomechanics is an important factor in the progression of ONFH. The decreased mechanical properties may be a direct reason leading to the late collapse of the femoral head. The treatment of ONFH should focus not only on acceleration of the bone healing, but also on provision of a favorable and stable biomechanical environment for the infected femoral head.