Quantification of lumbar spine load transfer is important for understanding low back pain, especially among persons with a lower limb amputation. Computational modeling provides a helpful solution for obtaining estimates of in vivo loads. A multiscale model was constructed by combining musculoskeletal and finite element (FE) models of the lumbar spine to determine tissue loading during daily activities. Three-dimensional kinematic and ground reaction force data were collected from participants with ([Formula: see text]) and without ([Formula: see text]) a unilateral transtibial amputation (TTA) during 5 sit-to-stand trials. We estimated tissue-level load transfer from the multiscale model by controlling the FE model with intervertebral kinematics and muscle forces predicted by the musculoskeletal model. Annulus fibrosis stress, intradiscal pressure (IDP), and facet contact forces were calculated using the FE model. Differences in whole-body kinematics, muscle forces, and tissue-level loads were found between participant groups. Notably, participants with TTA had greater axial rotation toward their intact limb ([Formula: see text]), greater abdominal muscle activity ([Formula: see text]), and greater overall tissue loading throughout sit-to-stand ([Formula: see text]) compared to able-bodied participants. Both normalized (to upright standing) and absolute estimates of L4-L5 IDP were close to in vivo values reported in the literature. The multiscale model can be used to estimate the distribution of loads within different lumbar spine tissue structures and can be adapted for use with different activities, populations, and spinal geometries.