Biomechanical models of the spine either simplify intervertebral joints (using spherical joints or deformable beams) in musculoskeletal (MS) or overlook musculature in geometrically-detailed passive finite element (FE) models. These distinct active and passive models therefore fail to determine in vivo stresses and strains within and load-sharing among the joint structures (discs, ligaments, and facets). A novel hybrid active–passive spine model is therefore developed in which estimated trunk muscle forces from a MS model for in vivo activities drive a mechanically-equivalent passive FE model to quantify in vivo T12–S1 compression/shear loads, intradiscal pressures (IDP), centers of rotation (CoR), ligament/facet forces, and annulus fiber strains. The predicted and in vivo L4–L5 IDP and L1–S1 CoRs showed satisfactory agreements. The FE model under commonly-used in vitro loading (pure moments and follower loads) predicted different kinetics from those of the hybrid model under in vivo loads (muscle exertions and gravity loads) contributing to suggest the inadequacy of such in vitro loads when simulating in vivo tasks. For an improved assessment of the injury risk, evaluation of the internal loads, and design of implants, such hybrid models should therefore be used. © 2018, Biomedical Engineering Society.