Changes in the sources of velocity anisotropy and their relative magnitude as maturation progresses in organic-rich shale are still incompletely characterized in the rock-physics literature. As a result of the increasing importance of organic-rich shale as unconventional reservoirs, a more thorough understanding of the elastic behavior of shale is needed. We have formulated a comprehensive, multiphysics, multiscale experimental methodology for the characterization of the intrinsic (syn-lithification) and extrinsic (postlithification) factors contributing to velocity anisotropy. Application of this methodology to unsaturated samples also enabled the characterization of the shale frame for fluid substitution modeling. The methodological framework was then tested on a set of five naturally matured organic-rich shale samples. In this experimental methodology, we combined classical rock-physics measurements, e.g., ultrasonic velocity and emergent high-resolution imaging techniques, such as X-ray diffraction (XRD), scanning electron microscopy, confocal laser scanning microscopy, and X-ray microtomography to better characterize the heterogeneous and microstructurally complex shale at all scales. The use of XRD-based lattice-preferred orientation measurements in conjunction with conventional ultrasonic velocity experiments confirmed that the degree of alignment of the mineral matrix governed the intrinsic anisotropy of organic-rich shale. The closure of soft, crack-like porosity, as identified from axial strain data, was identified as the extrinsic source governing the pressure sensitivity of velocity anisotropy. We determined, for the set of samples included in this study, that the intrinsic anisotropy was the dominant source of anisotropy at all confining pressures. Indeed, at low confining pressures, the opening of microcracks contributed no more than 30% of the total velocity anisotropy. Applying these results to saturated rocks at depth indicated that, for these shales, the extrinsic, crack-based sources, will contribute no more than 30% of the shale anisotropy in situ.