This study aimed to compare the microstructure and nanomechanical properties of single trabecular bone in different regions of osteonecrosis of the femoral head. Osteonecrotic femoral heads were taken from 20 patients undergoing total hip arthroplasties between 2011 and 2014. Following incision, resin was embedded and polished, and divided into four regions according to the type of pathologic change; i.e., subchondral bone, and necrotic, sclerotic, and healthy regions. Indents from a single trabecular bone of each region were randomly selected to undergo nanoindentation. The results are (1) The elastic modulus and degree of hardness were significantly elevated in the sclerotic region, but there were no differences in necrotic and subchondral bone regions compared with healthy regions. (2) The elastic modulus and hardness of the single trabecular bone were significantly greater in central versus edge regions (for all regions). The conclusions are (1) The mechanical properties of single bone trabeculae were not markedly altered in the necrotic region. (2) The elastic modulus and degree of hardness increased significantly between the edge and central regions, regardless of whether the bone was normal or osteonecrotic.