Overburden stresses and pore pressure are altered by depletion or inflation of a subsurface reservoir, leading to seismic traveltime and reflectivity changes that may be interpreted as footprints of reservoir drainage or injection. Our objective is to contribute to the quantification of expected 4D seismic time shifts and reflectivities by understanding how overburden stresses and strains change and how seismic velocities depend on these stress and strain changes. The stress sensitivity of ultrasonic velocities has been obtained from controlled laboratory experiments in which field shale cores are brought to in situ conditions and then probed with different stress paths, i.e., different ratios between the horizontal and vertical stress change. The tests are performed in undrained conditions, and pore-pressure changes are recorded. The experiments indicate that the velocity and pore-pressure changes depend linearly on the stress path. The latter is a verification of the applicability of Skempton’s law from soil mechanics for shales. Overburden stress paths are, through analytical and numerical geomechanical modeling, seen to depend on the aspect ratio of the depleting or inflating zone, on the elastic contrast between the overburden and the reservoir, and on the reservoir tilt. By combining laboratory data and simulated overburden stress paths, the response of in situ wave velocities to reservoir pore-pressure change can be estimated. The calculated in situ stress dependence of the vertical P-wave velocity shows significant dependence on stress path. The strain sensitivity, expressed by the dilation parameter, or factor, increases strongly with the stress path. This expresses the explicit sensitivity of to vertical in situ strain. The results also indicate that the time-lapse overburden response may be significantly influenced by pore-pressure changes in the overburden.