Abstract Background Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a promising technique for palliative treatment of bone pain. In this study, the effects of MR-HIFU ablation on bone mechanics and modeling were investigated. Methods A total of 12 healthy rat femurs were ablated using 10 W for 46 ± 4 s per sonication with 4 sonications for each femur. At 7 days after treatments, all animals underwent MR and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Then, six animals were euthanized. At 1 month following ablations, the remaining six animals were scanned again with MR and SPECT/CT prior to euthanization. Thereafter, both the HIFU-treated and contralateral control bones of three animals from each time interval were processed for histology, whereas the remaining bones were subjected to micro-CT (μCT), three-point bending tests, and micro-finite element (micro-FE) analyses. Results At 7 days after HIFU ablations, edema formation around the treated bones coupled with bone marrow and cortical bone necrosis was observed on MRI and histological images. SPECT/CT and μCT images revealed presence of bone modeling through an increased uptake of 99m Tc-MDP and formation of woven bone, respectively. At 31 days after ablations, as illustrated by imaging and histology, healing of the treated bone and the surrounding soft tissue was noted, marked by decreased in amount of tissue damage, formation of scar tissue, and sub-periosteal reaction. The results of three-point bending tests showed no significant differences in elastic stiffness, ultimate load, and yield load between the HIFU-treated and contralateral control bones at 7 days and 1 month after treatments. Similarly, the elastic stiffness and Young’s moduli determined by micro-FE analyses at both time intervals were not statistically different. Conclusions Multimodality imaging and histological data illustrated the presence of HIFU-induced bone damage at the cellular level, which activated the bone repair mechanisms. Despite that, these changes did not have a mechanical impact on the bone.