Bone-anchored limbs (BALs) are a transformative alternative for patients with lower-limb amputation who suffer from debilitating socket problems by eliminating the need for skin-to-prosthetic contact. Despite its successes, some individuals continue to face challenges with BALs, experiencing a loss of implant integration resulting in prosthetic loosening. A thorough understanding of biomechanical behavior at the residual limb and bone-implant interface is necessary to fully understand mechanical failure mechanisms. In addition, a deeper understanding of BAL biomechanical behavior would allow clinicians and researchers to predict and test different implant geometries, inform patient eligibility, rehabilitation strategies, and implantation methods in a safe and low-cost way. Thus, this study designed an innovative simulation method to quantify the temporal mechanical behavior of the residual limb in transfemoral and transtibial BALs by using subject-specific kinematics, musculoskeletal loads, and bone geometry and health. Our novel method was applied to two patients (one transtibial, one transfemoral) with similar BMI and age during level ground walking. Our results demonstrated a pattern of higher residual limb stresses in the transtibial model (26.80 MPa vs. 23.69 MPa). This study not only furthers our understanding of BAL biomechanics but introduces a versatile subject-specific methodology with direct applications in clinical practice. As we navigate the complexities of BAL implantation, this modeling platform lays the groundwork for more informed decision-making.